Spiropiperidines for use as tryptase inhibitors

ABSTRACT

The present invention is directed to a compound of Formula (I): 
     
       
         
         
             
             
         
       
     
     or a form thereof, wherein X 1 , X 2 , X 3 , X 4 , R 1 , R 2  and R 3  are as defined herein, useful as tryptase inhibitors.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. nonprovisional application Ser.No. 12/313,289, filed on Nov. 19, 2008, which claims benefit of priorityfrom U.S. provisional application Ser. No. 61/003,970, filed on Nov. 21,2007.

FIELD OF THE INVENTION

The present invention relates to certain spiropiperidine tryptaseinhibitor compounds, methods for preparing compounds, compositions,intermediates and derivatives thereof and methods for treating atryptase mediated disorder.

BACKGROUND OF THE INVENTION

Mast cells are a key cellular component of the inflammatory response andwhen activated, secrete numerous proinflammatory mediators, includinghistamine, arachidonic acid derivatives, and some serine proteases.Among these mast cell serine proteases are the unique carboxypeptidases,chymase and tryptase (Walls et al. Eur. J. Pharmacol. 1997, 328, 89-97).Active tryptase is a structurally unique trypsin-like serine proteasewhich exists as a tetramer that is stabilized by heparin proteoglycanswhich are stored and secreted with the enzyme (Bode et al. Nature 1998,392, 306-311). With the exception of neutrophil lactoferrin and possiblysecretory leukocyte proteinase inhibitor, tryptase is generally notaffected by endogenous serine protease inhibitors such as α2-macroglobin, α 2-proteinase inhibitor, aprotinin, and antithrombin. Itis postulated that in vivo tryptase activity may be regulated by thedissociation of the active tryptase tetramer into inactive monomers viathe removal of heparin.

Tryptase is secreted exclusively by mast cells and comprises up to 25%of the total protein of the mast cell (Schwartz et al., J. Clin. Invest.1989, 84, 1188-1195). Consequently, mast cell-derived tryptase issecreted in high concentrations at sites of tissue injury. Activatedmast cells in atherosclerotic/restenotic plaque have been implicated inplaque rupture and stenosis and are also manifested in inflamed tissuesof the gastrointestinal tract. Elevated tryptase levels have beendetected in bronchoalveolar lavage fluid (asthma), tears(conjunctivitis), blister fluids (dermatitis), blood (anaphylaxis),cerebrospinal fluid (multiple sclerosis), synovial fluid (rheumatoidarthritis) (Rice et al. Curr. Pharm. Design, 1998, 4, 381-396). Elevatedlevels of tryptase have also been found in diseased arteries(atherosclerotic, restenotic) relative to normal arteries. Somecigarette smokers have elevated bronchooalveolar lavage fluid tryptaselevels relative to nonsmokers, providing support for the hypothesis thatmast cell proteases may contribute to lung destruction in smoker'semphysema (Kalenderian et al. Chest 1998, 94, 119-123).

The potent bronchodilating neuropeptides, vasoactive intestinal peptide(VIP) and peptide histidine methionine (PHM) are readily cleaved bytryptase in vitro whereas substance P, a potent bronchoconstrictingpeptide, is not (Drazen et al. J. Clin. Invest 1993, 91, 235-243).Tryptase has demonstrated the ability to generate bradykinin, which isknown to induce bronchoconstriction in asthmatics (Zhang et al.Mediators of Inflammation. 1997, 6, 311-317). The ability of tryptase tostimulate inflammatory eosinophils and neutophil chemotaxis in vitro andin vivo is well known (Walls et al. J. Immunol. 1997, 159, 6216-6225).Inhaled tryptase has been shown to cause bronchoconstriction in sheepthrough the release of histamine (Abraham et al. Amer. J. of Respir. andCrit. Care Med. 1996, 154, 649-654). The ability of tryptase to directlystimulate mast cell degranulation in vitro and in animal models suggeststhat there may be a tryptase mediated amplification mechanism of theallergic inflammatory response (Walls et al. Eur. J. Pharmacol. 1997,328, 89-97).

Currently, only trypsin and tryptase are known to activate theprotease-activated receptor 2 (PAR-2), a cell surface G-protein-coupledreceptor. The activation of PAR-2 is primarily associated with theinduction of mitogenic response indicating that tryptase may have a rolein pathological conditions associated with tissue hyperplasia, includingthe airway hyperplasia found in chronic asthmatics (Stone et al. FEBSLetters 1997, 417, 267-269). Tryptase also has multiple effects onfibroblasts and there is in vitro evidence to suggest that tryptase mayinvolved in the early stages of fibrotic diseases, such as fibrotic lungdisease, schieroderma, atherosclerosis, and cardiomyopathic disorders(Marone et al. Circulation 1998, 97, 971-978). Hence, an inhibitor oftryptase could provide a novel therapeutic approach for the preventionand treatment of a variety of inflammatory diseases, such as vascularinjury (atherosclerosis, restenosis), arthritis, inflammatory boweldisease, Crohn's disease, dermatitis, urticaria, bullous pemphigoid,psoriasis, schleroderma, fibrosis, conjunctivitis, allergic rhinitis,and particularly asthma.

Asthma is the most common chronic disease in developed countries. Acomplex disease involving multiple biochemical mediators for both itsacute and chronic manifestations, asthma is frequently characterized bythe progressive development of hyperresponsiveness of the trachea andbronchi to both immunospecific allergens as well as generalized chemicalor physical stimuli. The hyperresponsiveness of asthmatic bronchiolartissue is postulated to result from chronic inflammation reactions,which irritate and damage the epithelium lining the airway wall andpromote pathological thickening of the underlying tissue. Bronchialbiopsy studies have indicated that even patients with mild asthma havefeatures of inflammation in the airway wall. Mast cells have long beenimplicated in the pathogenesis of asthma, particularly in the acuteresponse immediately after the exposure to allergen (Zhang et al.Mediators of Inflammation 1997, 6, 311-317).

The therapeutic strategy of employing tryptase inhibitors as a treatmentfor asthma in humans has been recently validated by the selectivetryptase inhibitor, APC-366 (Tanaka et al. Am. J. Respir. Crit. CareMed. 1995, 152, 2076-2083). A recent Phase IIa study was conducted with16 mild asthmatics who were dosed with either placebo or a nebulized drypowder formulation of APC-366 (Rice et al. Curr. Pharm. Design, 1998, 4,381-396). Compared with placebo, the same subjects had a statisticallysignificant improvement for the late airway response (33%; ρ=0.012) anda mean maximum decrease of forced expiratory volume in one second (21%;ρ=0.007) for late airway hyperresponsiveness. These positive resultsdemonstrate that tryptase inhibition is a promising approach for thetreatment of asthma in humans.

Currently, the most effective therapy for chronic asthma involvestreatment with glucocorticoids (Barnes New Engl. J. Med., 1995, 332,868-875). However, glucocorticoid administration also generates a litanyof local and systemic side-effects. Because of the limitations ofglucocorticoids, there is an unmet medical need for improved asthmatherapy. In contrast to drugs, such as steroids, that elicit multipleactions, tryptase inhibitors may elicit fewer side-effects through theselective inhibition of a specific inflammatory mediator (tryptase) thatis exclusive to mast cells. Hence, tryptase inhibitors may offer similarefficacy in the treatment of asthma as the glucocorticoids without thesame undesirable systemic side-effects.

International application WO 2005/058897 describes spiroindolinederivatives having insecticidal properties.

International application WO 2001/090101 describes arylmethylaminederivatives for use as tryptase inhibitors.

International application WO 2004/060884 describes(5-phenylethynyl-furan-2-yl)carbonyl substituted piperidinyl benzylaminecompounds for use as mast cell tryptase inhibitors.

International application WO 2005/095385 describes a process forpreparing (5-phenylethynyl-furan-2-yl)carbonyl substituted piperidinylbenzylamine compounds for use as tryptase inhibitors.

International application WO 2005/097780 describes(3-methyl-4-bromo-5-propoxy-thien-2-yl)carbonyl substituted piperidinylbenzylamine compounds for use as mast cell tryptase inhibitors.

SUMMARY OF THE INVENTION

The present invention is directed to a compound of Formula (I):

or a form thereof, wherein X₁, X₂, X₃, X₄, R₁, R₂ and R₃ are as definedherein, useful as tryptase inhibitors.

Illustrative of the invention is a pharmaceutical composition comprisinga pharmaceutically acceptable carrier and a compound of Formula (I).Also illustrative of the invention is a process for making apharmaceutical composition comprising mixing a compound of Formula (I)and a pharmaceutically acceptable carrier.

The present invention is further directed to methods for treating orameliorating a tryptase-mediated disorder. In particular, the method ofthe present invention is directed to treating or ameliorating atryptase-mediated disorder including, but not limited to, inflammatorydiseases associated with the respiratory tract, such as asthma andallergic rhinitis, as well as other immunomediated inflammatorydisorders, such as rheumatoid arthritis, conjunctivitis, psoriasis,inflammatory bowel disease, and various vascular or dermatologicalconditions.

Accordingly, it is an object of the present invention to providecompounds that are tryptase inhibitors useful for treating tryptasemediated disorders. It is another object of the invention to provide aprocess for preparing such spiro compounds, compositions, intermediatesand derivatives thereof.

It is a further object of the invention to provide a method for treatinga tryptase mediated inflammatory, vascular or dermatological conditionin a subject in need thereof comprising administering to the subject aneffective amount of a compound of Formula (I), wherein the inflammatory,vascular or dermatological condition is selected from, but not limitedto, inflammatory diseases associated with the respiratory tract, such asasthma and allergic rhinitis, as well as other immunomediatedinflammatory disorders, such as rheumatoid arthritis, rheumatoidspondylitis, osteoarthritis, gouty arthritis, peptic ulcers, ocular andvernal conjunctivitis, psoriasis, inflammatory bowel disease, Crohn'sdisease, chronic obstructive pulmonary disease, urticaria, bullouspemphiguoid, schleroderma, fibrosis, dermatitis, psoriasis, pruritis,angioedema, eczematous dermatitis, anaphylaxis, hyperproliferative skindisease, inflammatory skin conditions, hepatic cirrhosis,glomerulonephritis, nephritis, vascular inflammation, atherosclerosis orrestenosis.

Also included in the invention is the use of any of the compoundsdescribed above for the preparation of a medicament for treating atryptase mediated inflammatory, vascular or dermatological condition ina subject in need thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows changes in specific airway resistance in early phaseresponse to antigen challenge.

FIG. 2 shows late phase response and airway hyperreactivity to antigenchallenge.

FIG. 3 shows changes in early phase pulmonary responses as measured inPenH with whole body plethysmography following OVA challenge.

FIG. 4 shows changes in BAL immune cells following OVA challenge atvarious dose levels.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is directed to a compound of Formula (I):

or a form thereof, wherein

-   X₁ and X₂, respectively, are selected from the group consisting of    —CH₂— and —CH₂—, —CH₂— and —O—, —O— and —CH₂—, —CH₂— and —N(R₄)—,    —N(R₄)— and —CH₂—, —CH₂— and —S—, —S— and —CH₂—, —CH₂— and —S(O)—,    —S(O)— and —CH₂—, —CH₂— and —SO₂—, —SO₂— and —CH₂—, —C(O)— and    —CH₂—, —CH₂— and —C(O)—, —C(O)— and —N(R₄)—, —N(R₄)— and —C(O)—,    —C(O)— and —S— and —S— and —C(O)—;-   X₃ and X₄, respectively, are selected from the group consisting of    —CH₂— and —CH₂—, —CH₂— and —C(O)— and —C(O)— and —CH₂—;-   R₁ is selected from the group consisting of aminoC₁₋₄alkyl,    (C₁₋₄alkyl)aminoC₁₋₄alkyl, (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl,    (C₁₋₄alkyl)₃-aminoC₁₋₄alkyl, formylaminoC₁₋₄alkyl,    arylcarbonylaminoC₁₋₄alkyl, aminosulfonylaminoC₁₋₄alkyl,    arylC₁₋₄alkylaminoC₁₋₄alkyl, C₃₋₁₄cycloalkylcarbonylaminoC₁₋₄alkyl,    C₃₋₁₄cycloalkylC₁₋₄alkenylcarbonylaminoC₁₋₄alkyl,    arylC₁₋₄alkylcarbonylaminoC₁₋₄alkyl,    arylC₂₋₄alkenylcarbonylaminoC₁₋₄alkyl,    arylC₂₋₄alkynylcarbonylaminoC₁₋₄alkyl, arylsulfonylaminoC₁₋₄alkyl,    heterocyclylcarbonylaminoC₁₋₄alkyl,    heterocyclylC₁₋₄alkylcarbonylaminoC₁₋₄alkyl,    heterocyclylC₁₋₄alkenylcarbonylaminoC₁₋₄alkyl,    heteroarylcarbonylaminoC₁₋₄alkyl,    heteroarylC₂₋₄alkenylcarbonylaminoC₁₋₄alkyl, aminoimino,    hydroxyaminoimino, (C₁₋₄alkyl)aminoimino, (C₁₋₄alkyl)₂-aminoimino    and aminoaminoimino,-   wherein each instance of aryl is optionally substituted with one or    two halogen substituents;-   R₂ is absent or is one halogen substituent;-   R³ is hydrogen or is selected from the group consisting of    R⁵-arylC₁₋₄alkyl, carbonyl and sulfonyl,-   wherein carbonyl and sulfonyl are each substituted with a    substituent selected from the group consisting of R⁵-aryl,    R⁵-arylC₁₋₄alkyl, R⁵-arylC₁₋₄alkylamino, (R⁵-aryl)₁₋₂C₁₋₄alkyl,    R⁵-arylC₂₋₄alkenyl, R⁵-arylC₂₋₄alkynyl, R⁸—C₃₋₁₄cycloalkyl,    R⁸—C₃₋₁₄cycloalkylC₁₋₄alkyl, R⁶—C₃₋₁₄cycloalkylC₁₋₄alkenyl,    R⁷-heterocyclyl, R⁷-heterocyclylC₁₋₄alkyl,    R⁷-heterocyclylC₁₋₄alkenyl, R⁸-heteroaryl and    R⁸-heteroarylC₂₋₄alkenyl, wherein each instance of C₂₋₄alkenyl is    optionally substituted with one substituent selected from the group    consisting of halogen, cyano, C₁₋₄alkylcarbonylamino and aryl;-   R⁵ is one optional substituent selected from the group consisting of    R^(5a)-aryl, R^(5a)-arylC₁₋₄alkyl, R^(5a)-arylC₁₋₄alkoxy,    R^(5a)-aryloxy, R^(5a)-arylcarbonyl, R^(5a)-arylsulfonylamino,    R^(5b)-heteroaryl, R^(5b)-heteroarylC₁₋₄alkyl,    R^(5b)-heteroarylC₁₋₄alkylcarbonylamino, R^(5b)-heteroarylthio,    R^(5b)-heteroaryl-(R^(5b))-heteroaryl, R^(5b)-heterocyclyl and    C₃₋₁₄cycloalkyl, and-   one or two optional substituents each selected from the group    consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl,    C₂₋₄alkenyl, C₂₋₄alkynyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl,    C₁₋₄alkoxy, C₁₋₄alkoxyC₁₋₄alkyl, C₁₋₄alkoxyC₁₋₄alkoxy,    haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio, C₁₋₄alkylcarbonyl,    C₁₋₄alkoxycarbonyl, aminothiocarbonylamino, amino, (C₁₋₄alkyl)amino,    (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl,    (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl, aminocarbonyl, C₁₋₄alkylsulfonyl,    aminosulfonyl, (C₁₋₄alkyl)aminosulfonyl and    (C₁₋₄alkyl)₂-aminosulfonyl;-   R^(5a) is one, two or three optional substituents each selected from    the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl,    haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, haloC₁₋₄alkoxy,    C₁₋₄alkylthio, haloC₁₋₄alkylthio, amino, (C₁₋₄alkyl)amino,    (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl and    (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl;-   R^(5b) is one, two or three optional substituents each selected from    the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl,    haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, haloC₁₋₄alkoxy,    C₁₋₄alkylthio, haloC₁₋₄alkylthio, amino, (C₁₋₄alkyl)amino,    (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl and    (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl;-   R⁶ is one or two optional substituents each selected from the group    consisting of C₁₋₄alkyl, oxo and aryl;-   R⁷ is an optional substituent on one, two or three carbon atoms each    selected from the group consisting of halogen, C₁₋₄alkyl,    C₁₋₄alkoxy, C₁₋₄alkylthio, arylC₁₋₄alkylthio, oxo and aryl, and-   two optional substituents on one carbon atom each selected from the    group consisting of C₁₋₄alkyl and halogen, and-   one or two optional oxo substituents on a sulfur atom, when said    sulfur atom is present;-   R⁸ is an optional substituent on one carbon atom or an available    nitrogen atom selected from the group consisting of R^(8a)-aryl,    R^(8a)-arylC₁₋₄alkyl, R^(8a)-arylC₂₋₄alkenyl,    R^(8a)-arylC₂₋₄alkynyl, R^(8a)-aryloxy, R^(8a)-aryloxyC₁₋₄alkyl,    R^(8a)-arylthio, R^(8a)-arylC₁₋₄alkylthio,    R^(8a)-arylC₁₋₄alkylthioC₁₋₄alkyl, R^(8a)-arylsulfonyl,    R^(8b)-heteroaryl, R^(8b)-heteroarylC₁₋₄alkyl,    R^(8b)-heteroarylthioC₁₋₄alkyl,    R^(8b)-heteroarylcarbonylaminoC₁₋₄alkyl and    R^(8c)-heterocyclylC₁₋₄alkyl, and-   an optional C₁₋₄alkyl substituent on an available nitrogen atom, and-   an optional substituent on one, two or three carbon atoms each    selected from the group consisting of halogen, cyano, C₁₋₄alkyl,    haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, haloC₁₋₄alkoxy, formyl,    C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, C₁₋₄alkylthio and    C₁₋₄alkylsulfonyl;-   R^(8a) is one, two or three optional substituents each selected from    the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl,    C₂₋₄alkenyl, C₂₋₄alkynyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl,    C₁₋₄alkoxy, haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio,    C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, amino, (C₁₋₄alkyl)amino,    (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl and    (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl;-   R^(8b) is one, two or three optional substituents each selected from    the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl,    C₂₋₄alkenyl, C₂₋₄alkynyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl,    C₁₋₄alkoxy, haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio,    C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, amino, (C₁₋₄alkyl)amino,    (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl and    (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl;-   R₄ is one substituent selected from the group consisting of    hydrogen, C₁₋₄alkyl, carboxyC₁₋₄alkyl, C₁₋₄alkylcarbonyl,    C₁₋₄alkoxycarbonyl, C₁₋₄alkoxycarbonylC₁₋₄alkyl,    C₁₋₄alkoxycarbonylC₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonylcarbonyl,    aminocarbonyl, R⁹-arylC₁₋₄alkyl, R⁹-arylcarbonyl, hydroxysulfonyl,    aminosulfonyl, C₁₋₄alkylsulfonyl, hydroxysulfonylC₁₋₄alkylcarbonyl,    C₁₋₄alkylsulfonylC₁₋₄alkylcarbonyl,    C₁₋₄alkylsulfonylC₁₋₄alkylsulfonyl,    C₁₋₄alkoxycarbonylC₁₋₄alkylsulfonyl, R⁹-arylsulfonyl,    P[(O)(OH)₂]—C₁₋₄alkyl, R¹⁰-heterocyclylcarbonyl,    R¹⁰-heterocyclylsulfonyl, R¹¹-heteroarylcarbonyl,    R¹¹-heteroarylC₁₋₄alkylcarbonyl and R¹¹-heteroarylsulfonyl,-   wherein C₁₋₄alkoxycarbonylC₁₋₄alkylcarbonyl is optionally    substituted on C₁₋₄alkyl with (C₁₋₄alkyl)aminoamino;-   R⁹ is one or two optional substituents each selected from the group    consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl,    C₂₋₄alkenyl, C₂₋₄alkynyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl,    C₁₋₄alkoxy, carboxy, C₁₋₄alkoxyC₁₋₄alkyl, C₁₋₄alkoxyC₁₋₄alkoxy,    haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio, C₁₋₄alkylcarbonyl,    C₁₋₄alkoxycarbonyl, aminothiocarbonylamino, amino, (C₁₋₄alkyl)amino,    (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl,    (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl, aminocarbonyl, C₁₋₄alkylsulfonyl,    aminosulfonyl, (C₁₋₄alkyl)aminosulfonyl and    (C₁₋₄alkyl)₂-aminosulfonyl;-   R¹⁰ is an optional substituent on one, two or three carbon atoms    each selected from the group consisting of halogen, C₁₋₄alkyl,    C₁₋₄alkoxy, C₁₋₄alkylthio, (C₁₋₄alkyl)aminoamino and oxo, and-   two optional substituents on one carbon atom each selected from the    group consisting of C₁₋₄alkyl and halogen, and-   one or two optional oxo substituents on a sulfur atom, when said    sulfur atom is present; and-   R¹¹ is an optional C₁₋₄alkyl substituent on an available nitrogen    atom, and-   an optional substituent on one, two or three carbon atoms each    selected from the group consisting of halogen, cyano, C₁₋₄alkyl,    C₁₋₄alkoxy, haloC₁₋₄alkoxy, carboxy, formyl, C₁₋₄alkylcarbonyl,    C₁₋₄alkoxycarbonyl and C₁₋₄alkylthio.

An example of a compound of Formula (I) includes compounds or a formthereof, wherein

-   X₁ and X₂, respectively, are selected from the group consisting of    —CH₂— and —CH₂—, —CH₂— and —O—, —O— and —CH₂—, —CH₂— and —N(R₄)—,    —N(R₄)— and —CH₂—, —CH₂— and —S—, —S— and —CH₂—, —CH₂— and —S(O)—,    —S(O)— and —CH₂—, —CH₂— and —SO₂—, —SO₂— and —CH₂—, —C(O)— and    —CH₂—, —CH₂— and —C(O)—, —C(O)— and —N(R₄)—, —N(R₄)— and —C(O)—,    —C(O)— and —S— and —S— and —C(O)—;-   X₃ and X₄, respectively, are selected from the group consisting of    —CH₂— and —CH₂—, —CH₂— and —C(O)— and —C(O)— and —CH₂—;-   R₁ is selected from the group consisting of aminoC₁₋₄alkyl,    (C₁₋₄alkyl)aminoC₁₋₄alkyl, (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl,    (C₁₋₄alkyl)₃-aminoC₁₋₄alkyl, formylaminoC₁₋₄alkyl,    phenylcarbonylaminoC₁₋₄alkyl, aminosulfonylaminoC₁₋₄alkyl,    arylC₁₋₄alkylaminoC₁₋₄alkyl, C₃₋₁₄cycloalkylcarbonylaminoC₁₋₄alkyl,    C₃₋₁₄cycloalkylC₁₋₄alkenylcarbonylaminoC₁₋₄alkyl,    arylC₁₋₄alkylcarbonylaminoC₁₋₄alkyl,    arylC₂₋₄alkenylcarbonylaminoC₁₋₄alkyl,    arylC₂₋₄alkynylcarbonylaminoC₁₋₄alkyl, arylsulfonylaminoC₁₋₄alkyl,    heterocyclylcarbonylaminoC₁₋₄alkyl,    heterocyclylC₁₋₄alkylcarbonylaminoC₁₋₄alkyl,    heterocyclylC₁₋₄alkenylcarbonylaminoC₁₋₄alkyl,    heteroarylcarbonylaminoC₁₋₄alkyl,    heteroarylC₂₋₄alkenylcarbonylaminoC₁₋₄alkyl, aminoimino,    hydroxyaminoimino, (C₁₋₄alkyl)aminoimino, (C₁₋₄alkyl)₂-aminoimino    and aminoaminoimino,-   wherein each instance of phenyl is optionally substituted with one    or two halogen substituents;-   R₂ is absent or is one halogen substituent;-   R³ is hydrogen or is selected from the group consisting of    R⁵-phenylC₁₋₄alkyl, carbonyl and sulfonyl,-   wherein carbonyl and sulfonyl are each substituted with a    substituent selected from the group consisting of R⁵-phenyl,    R⁵-naphthalenyl, R⁵-phenyl-C₁₋₄alkyl, R⁵-naphthalenyl-C₁₋₄alkyl,    R⁶-fluorenyl-C₁₋₄alkyl, R⁵-phenyl-C₁₋₄alkylamino,    (R⁵-phenyl)₁₋₂C₁₋₄alkyl, R⁵-phenyl-C₂₋₄alkenyl,    R⁵-naphthalenyl-C₂₋₄alkenyl, R⁵-phenylC₂₋₄alkynyl, R⁶-cyclopropyl,    R⁶-indanyl, R⁶-1H-indenyl, R⁶-9H-fluorenyl,    R⁶—C₃₋₁₄cycloalkylC₁₋₄alkyl, R⁶-9H-fluorenyl-C₁₋₄alkenyl,    R⁷-benzo[1,3]dioxolyl, R⁷-4,5-dihydro-benzo[c]thiophenyl,    R⁷-4,5,6,7-tetrahydro-benzo[c]thiophenyl,    R⁷-4,5,6,7-tetrahydro-benzo[b]thiophenyl, R⁷-chromenyl,    R⁷-9H-xanthenyl, R⁷-9H-thioxanthenyl,    R⁷-5,6-dihydro-4H-cyclopenta[b]thiophenyl,    R⁷-4,5,6,7-tetrahydro-benzofuranyl,    R⁷-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophenyl,    R⁷-spiro[cyclohexane-1,6′-5,7-dihydro-4H-benzo[b]thiophene],    R⁷-benzo[1,3]dioxolyl-C₁₋₄alkyl, R⁷-benzo[1,3]dioxolyl-C₁₋₄alkenyl,    R⁷-3H-isobenzofuranyl-C₁₋₄alkenyl, R⁸-furanyl, R⁸-thienyl,    R⁸-thiazolyl, R⁸-[1,2,3]thiadiazolyl, R⁸-pyridinyl, R⁸-1H-indolyl,    R⁸-benzo[b]furanyl, R⁸-benzo[b]thiophenyl, R⁸-benzo[c]thiophenyl,    R⁸-1H-benzoimidazolyl, R⁸-benzothiazolyl,    R⁸-thieno[3,2-b]thiophenyl, R⁸-thieno[2,3-b]thiophenyl,    R⁸-naphtho[2,1-b]thiophenyl, R⁸-1H-thieno[2,3-c]pyrazolyl,    R⁸-imidazo[1,2-a]pyridinyl, R⁸-1H-imidazolyl-C₂₋₄alkenyl,    R⁸-furanyl-C₂₋₄alkenyl, R⁸-thienyl-C₂₋₄alkenyl and    R⁸-pyridinyl-C₂₋₄alkenyl, wherein each instance of C₂₋₄alkenyl is    optionally substituted with one substituent selected from the group    consisting of halogen, cyano, C₁₋₄alkylcarbonylamino and aryl;-   R⁵ is one optional substituent selected from the group consisting of    R^(5a)-phenyl, R^(5a)-phenylC₁₋₄alkyl, R^(5a)-phenylC₁₋₄alkoxy,    R^(5a)-phenoxy, R^(5a)-phenylcarbonyl, R^(5a)-phenylsulfonylamino,    R^(5b)-heteroaryl, R^(5b)-1H-benzoimidazolyl-C₁₋₄alkyl,    R^(5b)-1H-benzoimidazolyl-C₁₋₄alkylcarbonylamino,    R^(5b)-thienyl-C₁₋₄alkylcarbonylamino, R^(5b)-pyrimidinylthio,    R^(5b)-benzoxazolyl-(R^(5b))-pyrazolyl,    R^(5b)-thienyl-(R^(5b))-[1,2,4]oxadiazolyl,    R^(5b)-benzo[1,3]dioxolyl and cyclohexyl, and-   one or two optional substituents each selected from the group    consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl,    C₂₋₄alkenyl, C₂₋₄alkynyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl,    C₁₋₄alkoxy, C₁₋₄alkoxyC₁₋₄alkyl, C₁₋₄alkoxyC₁₋₄alkoxy,    haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio, C₁₋₄alkylcarbonyl,    C₁₋₄alkoxycarbonyl, aminothiocarbonylamino, amino, (C₁₋₄alkyl)amino,    (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl,    (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl, aminocarbonyl, C₁₋₄alkylsulfonyl,    aminosulfonyl, (C₁₋₄alkyl)aminosulfonyl and    (C₁₋₄alkyl)₂-aminosulfonyl;-   R^(5a) is one, two or three optional substituents each selected from    the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl,    haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, haloC₁₋₄alkoxy,    C₁₋₄alkylthio, haloC₁₋₄alkylthio, amino, (C₁₋₄alkyl)amino,    (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl and    (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl;-   R^(5b) is one, two or three optional substituents each selected from    the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl,    haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, haloC₁₋₄alkoxy,    C₁₋₄alkylthio, haloC₁₋₄alkylthio, amino, (C₁₋₄alkyl)amino,    (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl and    (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl;-   R⁶ is one or two optional substituents each selected from the group    consisting of C₁₋₄alkyl, oxo and phenyl;-   R⁷ is an optional substituent on one, two or three carbon atoms each    selected from the group consisting of halogen, C₁₋₄alkyl,    C₁₋₄alkoxy, C₁₋₄alkylthio, phenylC₁₋₄alkylthio, oxo and phenyl, and-   two optional substituents on one carbon atom each selected from the    group consisting of C₁₋₄alkyl and halogen, and-   one or two optional oxo substituents on a sulfur atom, when said    sulfur atom is present;-   R⁸ is an optional substituent on one carbon atom or an available    nitrogen atom selected from the group consisting of R^(8a)-phenyl,    R^(8a)-phenylC₁₋₄alkyl, R^(8a)-phenylC₂₋₄alkenyl,    R^(8a)-phenylC₂₋₄alkynyl, R^(8a)-naphthalenylC₂₋₄alkynyl,    R^(8a)-phenoxy, R^(8a)-phenoxyC₁₋₄alkyl, R^(8a)-phenylthio,    R^(8a)-phenylC₁₋₄alkylthio, R^(8a)-phenylC₁₋₄alkylthioC₁₋₄alkyl,    R^(8a)-phenylsulfonyl, R^(8b)-pyridinyl, R^(8b)-pyrazolyl,    R^(8b)-thienyl, R^(8b)-thiazolyl, R^(8b)-pyrazolylC₁₋₄alkyl,    R^(8b)-pyrimidinylthioC₁₋₄alkyl,    R^(8b)-furanylcarbonylaminoC₁₋₄alkyl and    R^(8c)-morpholinylC₁₋₄alkyl, and-   an optional C₁₋₄alkyl substituent on an available nitrogen atom, and-   an optional substituent on one, two or three carbon atoms each    selected from the group consisting of halogen, cyano, C₁₋₄alkyl,    haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, haloC₁₋₄alkoxy, formyl,    C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, C₁₋₄alkylthio and    C₁₋₄alkylsulfonyl;-   R^(8a) is one, two or three optional substituents each selected from    the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl,    C₂₋₄alkenyl, C₂₋₄alkynyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl,    C₁₋₄alkoxy, haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio,    C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, amino, (C₁₋₄alkyl)amino,    (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl and    (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl;-   R^(8b) is one, two or three optional substituents each selected from    the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl,    C₂₋₄alkenyl, C₂₋₄alkynyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl,    C₁₋₄alkoxy, haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio,    C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, amino, (C₁₋₄alkyl)amino,    (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl and    (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl;-   R₄ is one substituent selected from the group consisting of    hydrogen, C₁₋₄alkyl, carboxyC₁₋₄alkyl, C₁₋₄alkylcarbonyl,    C₁₋₄alkoxycarbonyl, C₁₋₄alkoxycarbonylC₁₋₄alkyl,    C₁₋₄alkoxycarbonylC₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonylcarbonyl,    aminocarbonyl, R⁹-phenyl-C₁₋₄alkyl, R⁹-phenyl-carbonyl,    hydroxysulfonyl, aminosulfonyl, C₁₋₄alkylsulfonyl,    hydroxysulfonylC₁₋₄alkylcarbonyl,    C₁₋₄alkylsulfonylC₁₋₄alkylcarbonyl,    C₁₋₄alkylsulfonylC₁₋₄alkylsulfonyl,    C₁₋₄alkoxycarbonylC₁₋₄alkylsulfonyl, R⁹-phenyl-sulfonyl,    P[(O)(OH)₂]-C₁₋₄alkyl, R¹⁰-tetrahydrothienyl-sulfonyl,    R¹¹-1H-tetrazolyl-carbonyl, R¹¹-1H-tetrazolyl-C₁₋₄alkylcarbonyl,    R¹¹-1H-imidazolyl-sulfonyl, R¹¹-furanyl-sulfonyl and    R¹¹-thienyl-sulfonyl,-   wherein C₁₋₄alkoxycarbonylC₁₋₄alkylcarbonyl is optionally    substituted on C₁₋₄alkyl with (C₁₋₄alkyl)aminoamino;-   R⁹ is one or two optional substituents each selected from the group    consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl,    C₂₋₄alkenyl, C₂₋₄alkynyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl,    C₁₋₄alkoxy, carboxy, C₁₋₄alkoxyC₁₋₄alkyl, C₁₋₄alkoxyC₁₋₄alkoxy,    haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio, C₁₋₄alkylcarbonyl,    C₁₋₄alkoxycarbonyl, aminothiocarbonylamino, amino, (C₁₋₄alkyl)amino,    (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl,    (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl, aminocarbonyl, C₁₋₄alkylsulfonyl,    aminosulfonyl, (C₁₋₄alkyl)aminosulfonyl and    (C₁₋₄alkyl)₂-aminosulfonyl;-   R¹⁰ is an optional substituent on one, two or three carbon atoms    each selected from the group consisting of halogen, C₁₋₄alkyl,    C₁₋₄alkoxy, C₁₋₄alkylthio, (C₁₋₄alkyl)aminoamino and oxo,-   two optional substituents on one carbon atom each selected from the    group consisting of C₁₋₄alkyl and halogen, and-   one or two optional oxo substituents on a sulfur atom, when said    sulfur atom is present;-   R¹¹ is an optional C₁₋₄alkyl substituent on an available nitrogen    atom, and-   an optional substituent on one, two or three carbon atoms each    selected from the group consisting of halogen, cyano, C₁₋₄alkyl,    C₁₋₄alkoxy, haloC₁₋₄alkoxy, carboxy, formyl, C₁₋₄alkylcarbonyl,    C₁₋₄alkoxycarbonyl and C₁₋₄alkylthio.

An example of a compound of Formula (I) includes compounds or a formthereof, wherein

-   X₁ and X₂, respectively, are selected from the group consisting of    —CH₂— and —CH₂—, —CH₂— and —O—, —CH₂— and —N(R₄)—, —CH₂— and —S—,    —C(O)— and —N(R₄)— and —N(R₄)— and —C(O)—;-   X₃ and X₄, respectively, are —CH₂— and —CH₂—;-   R₁ is selected from the group consisting of aminoC₁₋₄alkyl,    (C₁₋₄alkyl)aminoC₁₋₄alkyl, formylaminoC₁₋₄alkyl,    arylcarbonylaminoC₁₋₄alkyl, aminoimino, hydroxyaminoimino,    (C₁₋₄alkyl)aminoimino, (C₁₋₄alkyl)₂-aminoimino and aminoaminoimino,-   wherein each instance of aryl is optionally substituted with one or    two halogen substituents;-   R₂ is absent or is one halogen substituent;-   R³ is hydrogen or is selected from the group consisting of    R⁵-arylC₁₋₄alkyl, carbonyl and sulfonyl,-   wherein carbonyl and sulfonyl are each substituted with a    substituent selected from the group consisting of R⁵-aryl,    R⁵-arylC₁₋₄alkyl, R⁵-arylC₁₋₄alkylamino, (R⁵-aryl)₁₋₂C₁₋₄alkyl,    R⁵-arylC₂₋₄alkenyl, R⁵-arylC₂₋₄alkynyl, R⁸—C₃₋₁₄cycloalkyl,    R⁸—C₃₋₁₄cycloalkylC₁₋₄alkyl, R⁸—C₃₋₁₄cycloalkylC₁₋₄alkenyl,    R⁷-heterocyclyl, R⁷-heterocyclylC₁₋₄alkyl,    R⁷-heterocyclylC₁₋₄alkenyl, R⁸-heteroaryl and    R⁸-heteroarylC₂₋₄alkenyl, wherein each instance of C₂₋₄alkenyl is    optionally substituted with one substituent selected from the group    consisting of halogen, cyano, C₁₋₄alkylcarbonylamino and aryl;-   R⁵ is one optional substituent selected from the group consisting of    R^(5a)-aryl, R^(5a)-arylC₁₋₄alkyl, R^(5a)-arylC₁₋₄alkoxy,    R^(5a)-aryloxy, R^(5a)-arylcarbonyl, R^(5a)-arylsulfonylamino,    R^(5b)-heteroaryl, R^(5b)-heteroarylC₁₋₄alkyl,    R^(5b)-heteroarylC₁₋₄alkylcarbonylamino, R^(5b)-heteroarylthio,    R^(5b)-heteroaryl-(R^(5b))-heteroaryl, R^(5b)-heterocyclyl and    C₃₋₁₄cycloalkyl, and-   one or two optional substituents each selected from the group    consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl,    C₂₋₄alkenyl, haloC₁₋₄alkyl, C₁₋₄alkoxy, C₁₋₄alkoxyC₁₋₄alkoxy,    haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio, C₁₋₄alkylcarbonyl,    C₁₋₄alkoxycarbonyl, aminothiocarbonylamino, (C₁₋₄alkyl)₂-amino,    aminocarbonyl, C₁₋₄alkylsulfonyl and aminosulfonyl;-   R^(5a) is one or two optional substituents each selected from the    group consisting of halogen, C₁₋₄alkyl, haloC₁₋₄alkyl and    C₁₋₄alkoxy;-   R^(5b) is one or two optional halogen substituents;-   R⁶ is one optional substituent selected from the group consisting of    C₁₋₄alkyl, oxo and aryl;-   R⁷ is an optional substituent on one, two or three carbon atoms each    selected from the group consisting of halogen, C₁₋₄alkyl,    C₁₋₄alkoxy, C₁₋₄alkylthio, arylC₁₋₄alkylthio, oxo and aryl, and-   two optional C₁₋₄alkyl substituents on one carbon atom, and-   two oxo substituents on a sulfur atom, when said sulfur atom is    present;-   R⁸ is an optional substituent on one carbon atom or an available    nitrogen atom selected from the group consisting of R^(8a)-aryl,    R^(8a)-arylC₁₋₄alkyl, R^(8a)-arylC₂₋₄alkenyl,    R^(8a)-arylC₂₋₄alkynyl, R^(8a)-aryloxy, R^(8a)-aryloxyC₁₋₄alkyl,    R^(8a)-arylthio, R^(8a)-arylC₁₋₄alkylthio,    R^(8a)-arylC₁₋₄alkylthioC₁₋₄alkyl, R^(8a)-arylsulfonyl,    R^(8b)-heteroaryl, R^(8b)-heteroarylC₁₋₄alkyl,    R^(8b)-heteroarylthioC₁₋₄alkyl,    R^(8b)-heteroarylcarbonylaminoC₁₋₄alkyl and    R^(8c)-heterocyclylC₁₋₄alkyl, and-   an optional C₁₋₄alkyl substituent on an available nitrogen atom, and-   an optional substituent on one, two or three carbon atoms each    selected from the group consisting of halogen, cyano, C₁₋₄alkyl,    haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, formyl,    C₁₋₄alkoxycarbonyl, C₁₋₄alkylthio and C₁₋₄alkylsulfonyl;-   R^(8a) is one or two optional substituents each selected from the    group consisting of halogen, C₁₋₄alkyl, C₂₋₄alkenyl, haloC₁₋₄alkyl    and C₁₋₄alkoxy;-   R^(8b) is one, two or three optional substituents each selected from    the group consisting of halogen, C₁₋₄alkyl and haloC₁₋₄alkyl;-   R₄ is one substituent selected from the group consisting of    hydrogen, C₁₋₄alkyl, carboxyC₁₋₄alkyl, C₁₋₄alkylcarbonyl,    C₁₋₄alkoxycarbonyl, C₁₋₄alkoxycarbonylC₁₋₄alkyl,    C₁₋₄alkoxycarbonylC₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonylcarbonyl,    aminocarbonyl, R⁹-arylcarbonyl, hydroxysulfonyl, aminosulfonyl,    C₁₋₄alkylsulfonyl, hydroxysulfonylC₁₋₄alkylcarbonyl,    C₁₋₄alkylsulfonylC₁₋₄alkylcarbonyl,    C₁₋₄alkylsulfonylC₁₋₄alkylsulfonyl,    C₁₋₄alkoxycarbonylC₁₋₄alkylsulfonyl, R⁹-arylsulfonyl,    P[(O)(OH)₂]-C₁₋₄alkyl, R¹⁰-heterocyclylcarbonyl,    R¹⁰-heterocyclylsulfonyl, R¹¹-heteroarylcarbonyl,    R¹¹-heteroarylC₁₋₄alkylcarbonyl and R¹¹-heteroarylsulfonyl,-   wherein C₁₋₄alkoxycarbonylC₁₋₄alkylcarbonyl is optionally    substituted on C₁₋₄alkyl with (C₁₋₄alkyl)aminoamino;-   R⁹ is one or two optional substituents each selected from the group    consisting of C₁₋₄alkoxy, carboxy and C₁₋₄alkoxycarbonyl;-   R¹⁰ is an optional (C₁₋₄alkyl)aminoamino substituent on one carbon    atom, and-   two oxo substituents on a sulfur atom, when said sulfur atom is    present; and-   R¹¹ is an optional C₁₋₄alkyl substituent on an available nitrogen    atom, and-   an optional substituent on one carbon atom selected from the group    consisting of carboxy and C₁₋₄alkoxycarbonyl.

An example of a compound of Formula (I) includes compounds or a formthereof, wherein

-   X₁ and X₂, respectively, are selected from the group consisting of    —CH₂— and —CH₂—, —CH₂— and —O—, —CH₂— and —N(R₄)—, —CH₂— and —S—,    —C(O)— and —N(R₄)— and —N(R₄)— and —C(O)—;-   X₃ and X₄, respectively, are —CH₂— and —CH₂—;-   R₁ is selected from the group consisting of aminoC₁₋₄alkyl,    (C₁₋₄alkyl)aminoC₁₋₄alkyl, formylaminoC₁₋₄alkyl,    phenylcarbonylaminoC₁₋₄alkyl, aminoimino, hydroxyaminoimino,    (C₁₋₄alkyl)aminoimino, (C₁₋₄alkyl)₂-aminoimino and aminoaminoimino,-   wherein each instance of phenyl is optionally substituted with one    or two halogen substituents;-   R₂ is absent or is one halogen substituent;-   R³ is hydrogen or is selected from the group consisting of    R⁵-phenylC₁₋₄alkyl, carbonyl and sulfonyl,-   wherein carbonyl and sulfonyl are each substituted with a    substituent selected from the group consisting of R⁵-phenyl,    R⁵-naphthalenyl, R⁵-phenyl-C₁₋₄alkyl, R⁵-naphthalenyl-C₁₋₄alkyl,    R⁶-fluorenyl-C₁₋₄alkyl, R⁵-phenyl-C₁₋₄alkylamino,    (R⁵-phenyl)₁₋₂C₁₋₄alkyl, R⁵-phenyl-C₂₋₄alkenyl,    R⁵-naphthalenyl-C₂₋₄alkenyl, R⁵-phenylC₂₋₄alkynyl, R⁶-cyclopropyl,    R⁶-indanyl, R⁶-1H-indenyl, R⁶-9H-fluorenyl,    R⁶—C₃₋₁₄cycloalkylC₁₋₄alkyl, R⁶-9H-fluorenyl-C₁₋₄alkenyl,    R⁷-benzo[1,3]dioxolyl, R⁷-4,5-dihydro-benzo[c]thiophenyl,    R⁷-4,5,6,7-tetrahydro-benzo[c]thiophenyl,    R⁷-4,5,6,7-tetrahydro-benzo[b]thiophenyl, R⁷-chromenyl,    R⁷-9H-xanthenyl, R⁷-9H-thioxanthenyl,    R⁷-5,6-dihydro-4H-cyclopenta[b]thiophenyl,    R⁷-4,5,6,7-tetrahydro-benzofuranyl,    R⁷-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophenyl,    R⁷-spiro[cyclohexane-1,6′-5,7-dihydro-4H-benzo[b]thiophene],    R⁷-benzo[1,3]dioxolyl-C₁₋₄alkyl, R⁷-benzo[1,3]dioxolyl-C₁₋₄alkenyl,    R⁷-3H-isobenzofuranyl-C₁₋₄alkenyl, R⁸-furanyl, R⁸-thienyl,    R⁸-thiazolyl, R⁸-[1,2,3]thiadiazolyl, R⁸-pyridinyl, R⁸-1H-indolyl,    R⁸-benzo[b]furanyl, R⁸-benzo[b]thiophenyl, R⁸-benzo[c]thiophenyl,    R⁸-1H-benzoimidazolyl, R⁸-benzothiazolyl,    R⁸-thieno[3,2-b]thiophenyl, R⁸-thieno[2,3-b]thiophenyl,    R⁸-naphtho[2,1-b]thiophenyl, R⁸-1H-thieno[2,3-c]pyrazolyl,    R⁸-imidazo[1,2-a]pyridinyl, R⁸-1H-imidazolyl-C₂₋₄alkenyl,    R⁸-furanyl-C₂₋₄alkenyl, R⁸-thienyl-C₂₋₄alkenyl and    R⁸-pyridinyl-C₂₋₄alkenyl, wherein each instance of C₂₋₄alkenyl is    optionally substituted with one substituent selected from the group    consisting of halogen, cyano, C₁₋₄alkylcarbonylamino and aryl;-   R⁵ is one optional substituent selected from the group consisting of    R^(5a)-phenyl, R^(5a)-phenylC₁₋₄alkyl, R^(5a)-phenylC₁₋₄alkoxy,    R^(5a)-phenoxy, R^(5a)-phenylcarbonyl, R^(5a)-phenylsulfonylamino,    R^(5b)-1H-benzoimidazolyl-C₁₋₄alkyl,    R^(5b)-1H-benzoimidazolyl-C₁₋₄alkylcarbonylamino,    R^(5b)-thienyl-C₁₋₄alkylcarbonylamino, R^(5b)-pyrimidinylthio,    R^(5b)-benzoxazolyl-(R^(5b))-pyrazolyl,    R^(5b)-thienyl-(R^(5b))-[1,2,4]oxadiazolyl,    R^(5b)-benzo[1,3]dioxolyl and cyclohexyl, and-   one or two optional substituents each selected from the group    consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl,    C₂₋₄alkenyl, haloC₁₋₄alkyl, C₁₋₄alkoxy, C₁₋₄alkoxyC₁₋₄alkoxy,    haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio, C₁₋₄alkylcarbonyl,    C₁₋₄alkoxycarbonyl, aminothiocarbonylamino, (C₁₋₄alkyl)₂-amino,    aminocarbonyl, C₁₋₄alkylsulfonyl and aminosulfonyl;-   R^(5a) is one or two optional substituents each selected from the    group consisting of halogen, C₁₋₄alkyl, haloC₁₋₄alkyl and    C₁₋₄alkoxy;-   R^(5b) is one or two optional halogen substituents;-   R⁶ is one optional substituent selected from the group consisting of    C₁₋₄alkyl, oxo and phenyl;-   R⁷ is an optional substituent on one, two or three carbon atoms each    selected from the group consisting of halogen, C₁₋₄alkyl,    C₁₋₄alkoxy, C₁₋₄alkylthio, arylC₁₋₄alkylthio, oxo and phenyl, and-   two optional C₁₋₄alkyl substituents on one carbon atom, and-   two optional oxo substituents on a sulfur atom, when said sulfur    atom is present;-   R⁸ is an optional substituent on one carbon atom or an available    nitrogen atom selected from the group consisting of R^(8a)-phenyl,    R^(8a)-phenylC₁₋₄alkyl, R^(8a)-phenylC₂₋₄alkenyl,    R^(8a)-phenylC₂₋₄alkynyl, R^(8a)-naphthalenylC₂₋₄alkynyl,    R^(8a)-phenoxy, R^(8a)-phenoxyC₁₋₄alkyl, R^(8a)-phenylthio,    R^(8a)-arylC₁₋₄alkylthio, R^(8a)-phenylC₁₋₄alkylthioC₁₋₄alkyl,    R^(8a)-phenylsulfonyl, R^(8b)-pyridinyl, R^(8b)-pyrazolyl,    R^(8b)-thienyl, R^(8b)-thiazolyl, R^(8b)-pyrazolylC₁₋₄alkyl,    R^(8b)-pyrimidinylthioC₁₋₄alkyl,    R^(8b)-furanylcarbonylaminoC₁₋₄alkyl and    R^(8c)-morpholinylC₁₋₄alkyl, and-   an optional C₁₋₄alkyl substituent on an available nitrogen atom, and-   an optional substituent on one, two or three carbon atoms each    selected from the group consisting of halogen, cyano, C₁₋₄alkyl,    haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, formyl,    C₁₋₄alkoxycarbonyl, C₁₋₄alkylthio and C₁₋₄alkylsulfonyl;-   R^(8a) is one or two optional substituents each selected from the    group consisting of halogen, C₁₋₄alkyl, C₂₋₄alkenyl, haloC₁₋₄alkyl    and C₁₋₄alkoxy;-   R^(8b) is one, two or three optional substituents each selected from    the group consisting of halogen, C₁₋₄alkyl and haloC₁₋₄alkyl;-   R₄ is one substituent selected from the group consisting of    hydrogen, C₁₋₄alkyl, carboxyC₁₋₄alkyl, C₁₋₄alkylcarbonyl,    C₁₋₄alkoxycarbonyl, C₁₋₄alkoxycarbonylC₁₋₄alkyl,    C₁₋₄alkoxycarbonylC₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonylcarbonyl,    aminocarbonyl, R⁹-phenyl-C₁₋₄alkyl, R⁹-phenyl-carbonyl,    hydroxysulfonyl, aminosulfonyl, C₁₋₄alkylsulfonyl,    hydroxysulfonylC₁₋₄alkylcarbonyl,    C₁₋₄alkylsulfonylC₁₋₄alkylcarbonyl,    C₁₋₄alkylsulfonylC₁₋₄alkylsulfonyl,    C₁₋₄alkoxycarbonylC₁₋₄alkylsulfonyl, R⁹-phenyl-sulfonyl,    P[(O)(OH)₂]-C₁₋₄alkyl, R¹⁰-heterocyclylcarbonyl,    R¹⁰-tetrahydrothienyl-sulfonyl, R¹¹-1H-tetrazolyl-carbonyl,    R¹¹-1H-tetrazolyl-C₁₋₄alkylcarbonyl and R¹¹-1H-imidazolyl-sulfonyl,    R¹¹-furanyl-sulfonyl, R¹¹-thienyl-sulfonyl,-   wherein C₁₋₄alkoxycarbonylC₁₋₄alkylcarbonyl is optionally    substituted on C₁₋₄alkyl with (C₁₋₄alkyl)aminoamino;-   R⁹ is one or two optional substituents each selected from the group    consisting of C₁₋₄alkoxy, carboxy and C₁₋₄alkoxycarbonyl;-   R¹⁰ is an optional (C₁₋₄alkyl)aminoamino substituent on one carbon    atom, and-   two oxo substituents on a sulfur atom, when said sulfur atom is    present; and-   R¹¹ is an optional C₁₋₄alkyl substituent on an available nitrogen    atom, and-   an optional substituent on one carbon atom selected from the group    consisting of carboxy and C₁₋₄alkoxycarbonyl.

An example of a compound of Formula (I) includes compounds or a formthereof, wherein

-   X₁ and X₂, respectively, are selected from the group consisting of    —CH₂— and —CH₂—, —CH₂— and —O—, —CH₂— and —N(R₄)— and —N(R₄)— and    —C(O)—;-   X₃ and X₄, respectively, are —CH₂— and —CH₂—;-   R₁ is selected from the group consisting of aminoC₁₋₄alkyl and    aminoimino,-   R₂ is absent;-   R³ is carbonyl substituted with a substituent selected from the    group consisting of R⁵-aryl, R⁷-heterocyclyl and R⁸-heteroaryl;-   R⁵ is heteroaryl-heteroaryl, and-   an optional aminocarbonyl substituent;-   R⁷ is an optional substituent on one or two carbon atoms each    selected from the group consisting of C₁₋₄alkylthio,    arylC₁₋₄alkylthio and oxo;-   R⁸ is an optional substituent on one carbon atom selected from the    group consisting of R^(8a)-aryl, R^(8a)-arylC₂₋₄alkynyl and    R^(8a)-arylC₁₋₄alkylthio, and-   an optional substituent on one, two or three carbon atoms each    selected from the group consisting of halogen, C₁₋₄alkyl, C₁₋₄alkoxy    and C₁₋₄alkylthio;-   R^(8a) is one or two optional substituents each selected from the    group consisting of halogen and C₁₋₄alkyl;-   R₄ is one substituent selected from the group consisting of    hydrogen, aminosulfonyl, C₁₋₄alkylsulfonyl and arylsulfonyl.

An example of a compound of Formula (I) includes compounds or a formthereof, wherein

-   X₁ and X₂, respectively, are selected from the group consisting of    —CH₂— and —CH₂—, —CH₂— and —O—, —CH₂— and —N(R₄)— and —N(R₄)— and    —C(O)—;-   X₃ and X₄, respectively, are —CH₂— and —CH₂—;-   R₁ is selected from the group consisting of aminoC₁₋₄alkyl and    aminoimino,-   R₂ is absent;-   R³ is carbonyl substituted with a substituent selected from the    group consisting of R⁵-phenyl, R⁷-4,5-dihydro-benzo[c]thiophenyl,    R⁷-4,5,6,7-tetrahydro-benzo[c]thiophenyl, R⁸-furanyl, R⁸-thienyl,    R⁸-pyridinyl and R⁸-benzo[c]thiophenyl;-   R⁵ is thienyl-[1,2,4]oxadiazolyl, and-   an optional aminocarbonyl substituent;-   R⁷ is an optional substituent on one or two carbon atoms each    selected from the group consisting of C₁₋₄alkylthio,    phenylC₁₋₄alkylthio and oxo;-   R⁸ is an optional substituent on one carbon atom selected from the    group consisting of R^(8a)-phenyl, R^(8a)-phenylC₂₋₄alkynyl and    R^(8a)-phenylC₁₋₄alkylthio, and-   an optional substituent on one, two or three carbon atoms each    selected from the group consisting of halogen, C₁₋₄alkyl, C₁₋₄alkoxy    and C₁₋₄alkylthio;-   R^(8a) is one or two optional substituents each selected from the    group consisting of halogen and C₁₋₄alkyl;-   R₄ is one substituent selected from the group consisting of    hydrogen, aminosulfonyl, C₁₋₄alkylsulfonyl and arylsulfonyl.

An example of a compound of Formula (I) includes compounds or a formthereof, wherein

-   X₁ and X₂, respectively, are selected from the group consisting of    —CH₂— and —CH₂—, —CH₂— and —O—, —CH₂— and —N(R₄)— and —N(R₄)— and    —C(O)—;-   X₃ and X₄, respectively, are —CH₂— and —CH₂—;-   R₁ is selected from the group consisting of aminomethyl and    aminoimino,-   R₂ is absent;-   R³ is carbonyl substituted with a substituent selected from the    group consisting of R⁵-phenyl, R⁷-4,5-dihydro-benzo[c]thiophenyl,    R⁷-4,5,6,7-tetrahydro-benzo[c]thiophenyl, R⁸-furanyl, R⁸-thienyl,    R⁸-pyridinyl and R⁸-benzo[c]thiophenyl;-   R⁵ is thienyl-[1,2,4]oxadiazolyl, and-   an optional aminocarbonyl substituent;-   R⁷ is an optional substituent on one or two carbon atoms each    selected from the group consisting of methylthio, butylthio,    phenylmethylthio and oxo;-   R⁸ is an optional substituent on one carbon atom selected from the    group consisting of R^(8a)-phenyl, R^(8a)-phenylethynyl and    R^(8a)-phenylmethylthio, and-   an optional substituent on one, two or three carbon atoms each    selected from the group consisting of bromo, methyl, methoxy,    propoxy and methylthio;-   R^(8a) is one or two optional substituents each selected from the    group consisting of chloro, fluoro and methyl; and-   R₄ is one substituent selected from the group consisting of    hydrogen, aminosulfonyl, methylsulfonyl and phenylsulfonyl.

An example of a compound of Formula (I) includes compounds or a formthereof, wherein

-   X₁ and X₂, respectively, are selected from the group consisting of    —CH₂— and —CH₂—, —CH₂— and —O—, —CH₂— and —N(R₄)— and —N(R₄)— and    —C(O)—;-   X₃ and X₄, respectively, are —CH₂— and —CH₂—;-   R₁ is selected from the group consisting of aminomethyl and    aminoimino;-   R₂ is absent;-   R³ is selected from the group consisting of    (5-phenylethynyl-furan-2-yl)carbonyl,    [5-(2-fluoro-phenylethynyl)-furan-2-yl]carbonyl,    [5-(2-chloro-phenylethynyl)-furan-2-yl]carbonyl,    [4-phenylethynyl-pyridin-2-yl]carbonyl,    [5-(2-methyl-phenylethynyl)-furan-2-yl]carbonyl,    [5-(4-methyl-phenylethynyl)-furan-2-yl]carbonyl,    [5-(2,5-dimethyl-phenylethynyl)-furan-2-yl]carbonyl,    (3-benzylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl,    (3-butylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl,    (3-methylthio-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl,    (3-methylthio-7-hydro-6H-benzo[c]thien-1-yl)carbonyl,    (3-methylthio-benzo[c]thien-1-yl)carbonyl,    (3-methylthio-4-methoxy-benzo[c]thien-1-yl)carbonyl,    (3-benzylthio-benzo[c]thien-1-yl)carbonyl,    (3-benzylthio-7-hydro-6H-benzo[c]thien-1-yl)carbonyl,    (3-thien-2-yl-[1,2,4]oxadiazol-5-yl)carbonyl,    [3-(3-thien-2-yl-[1,2,4]oxadiazol-5-yl)-5-aminocarbonyl-phenyl]carbonyl    and (3-methyl-4-bromo-5-propoxy-thien-2-yl)carbonyl; and-   R₄ is one substituent selected from the group consisting of    hydrogen, aminosulfonyl, methylsulfonyl and phenylsulfonyl.

An example of a compound of Formula (I) includes compounds or a formthereof selected from the group consisting of:

A representative compound of Formula (I) or a form thereof includes acompound selected from the group consisting of:

Cpd Name 11-(3,4-dichlorophenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 25′-(3,4-dichlorophenylcarbonylaminomethyl)-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 31-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 41-(3-benzoyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 51-(3-aminothiocarbonylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 61-(4-benzoyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 71-(9-oxo-10,10-dioxo-thioxanthen-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 81-(9-oxo-fluoren-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 91-(4-benzoimidazol-1-ylmethylcarbonylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 101-(4-benzoimidazol-1-ylmethyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 111-(4-aminosulfonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 121-[5-(4-chloro-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 131-(5-chloro-benzo[b]-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 141-(1-phenyl-2-methyl-benzoimidazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 151-[4-(3-trifluoromethyl-phenyl)-phenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 161-benzothiazol-6-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 171-{4-[(4-benzoxazol-2-yl)-pyrazol-1-yl]-phenyl}carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 181-(3-phenylsulfonylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 191-(3-thien-2-ylmethylcarbonylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 201-(3-benzodioxol-5-yl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 211-[3-(5-chloro-pyrimidin-2-yl)thiophenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 221-(5-trifluoromethyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 231-[(5-phenylthio)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 241-(3,4-dimethyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 251-(3-methyl-4-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 261-(3,4-difluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 271-(3-chloro-4-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 281-(3-chloro-4-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 291-(3-bromo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 301-(3-methyl-4-bromo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 311-(3-bromo-4-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 321-(3-bromo-4-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 331-(3-nitro-4-bromo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 341-(3-iodo-4-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 351-[5-(2-fluoro-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 361-phenylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan],37 1-cyclohexylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 381-(trans-4-methyl-cyclohexyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 391-(3-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 401-(3,4-dimethoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 411-(3-methyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 421-(3-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 431-(4-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 441-(4-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 451-(4-methylthio-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 461-(3-fluoro-4-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 471-(3-trifluoromethyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 481-(3-iodo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 491-(4-iodo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 501-(3-iodo-4-methyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 511-(3-methyl-4-iodo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 521-(3-iodo-4-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 531-(3-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 541-(4-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 551-(4-dimethylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 561-(3-dimethylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 571-(3-methylthio-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 581-(4-methoxycarbonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 591-(4-bromo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 601-(3-trifluoromethoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 611-(4-trifluoromethoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 621-(4-phenoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 631-(3-trifluoromethylthio-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 641-[3-(4-methoxy-phenyl)-phenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 651-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminoiminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 661-(3-cyano-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 671-(4-methylcarbonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 681-benzodioxol-5-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 691-(4-chloromethyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 701-naphthalen-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 711-(4-trifluoromethyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 721-(3-methylsulfonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 731-(4-cyclohexyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 741-(3-trifluoromethyl-4-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 751-(4-benzyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 761-(4-benzyloxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 77(Z)-1-(5-phenylethenyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 781-benzylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan],79 1-phenethylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 801-(3-fluoro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 811-(3-chloro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 821-(3,4-difluoro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 831-(3-chloro-phenethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 841-naphthalen-2-ylmethylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 851-(3-trifluoromethyl-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 861-(3,4-dichloro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 871-(3-bromo-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 881-(3-phenoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 891-(3-methyl-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 901-(4-fluoro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 911-(4-chloro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 921-(4-phenyl-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 931-(4-bromo-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 941-(4-methoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 951-(3-bromo-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 961-(4-iodo-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 971-(3-iodo-phenethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 981-(3-methyl-phenethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 991-(3-methoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1001-benzodioxol-5-ylmethylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1011-(3-methoxy-phenethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1021-(3-methyl-4-methoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1031-(3-methylthio-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1041-(benzodioxol-5-ylethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1051-(3,4-dimethoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1061-(3-methoxy-4-benzyloxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1071-(5-phenethyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1081-(phenylethynyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 109(E)-1-(phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1101-benzothien-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 111(E)-1-(3,4-difluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 112(E)-1-(phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 113(E)-1-(naphthalene-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1141-(5-phenyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1151-(3-phenoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 116(E)-1-(3,4-dichloro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 117(E)-1-(4-phenyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1181-(2,4-dimethyl-thiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1191-(6-methyl-imidazo[1,2-a]pyridin-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1201-(5-pyridin-2-yl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1211-(2-pyridin-3-yl-thiazol-4-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1221-(2-pyridin-4-yl-thiazol-4-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1231-(2-phenyl-4-methyl-thiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1241-(2-pyridin-3-yl-4-methyl-thiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1251-[2-(4-methyl-phenyl)-4-methyl-thiazol-5-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1261-(6-bromo-naphthalen-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1271-[5-(1-methyl-3-trifluoromethyl-pyrazol-5-yl)-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1281-[2-(4-trifluoromethyl-phenyl)-4-methyl-thiazol-5-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1291-[5-(2-chloro-5-trifluoromethyl-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1301-(5-phenyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1311-[5-(4-methyl-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1321-[5-(4-methoxy-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1331-(3,5-di-tert-butyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1341-[5-(3-chloro-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1351-[5-(3-trifluoromethyl-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1361-[5-(2,4-dichloro-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1371-[5-(2,5-dichloro-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1381-[5-(3,4-dichloro-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1391-[5-(3-methyl-4-chloro-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1401-[5-(4-bromo-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1411-(trans-2-phenyl-cyclopropyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1421-(5-phenyl-pyridin-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1431-(5-thien-2-yl-pyridin-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1441-[5-(3-methoxy-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1451-[5-(4-chloro-pyrazol-1-ylmethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1461-[5-(2-chloro-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1471-[5-(benzylthiomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1481-[5-(4,6-dimethyl-pyrimidin-2-ylthiomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1491-[5-(3,5-dichloro-phenoxy)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1501-[5-(3,5-dimethyl-4-bromo-pyrazol-1-yl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1511-[5-(5-trifluoromethyl-pyridin-2-ylthiomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1521-[4-phenylethynyl-pyridin-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1531-[5-(2-methyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1541-[5-(4-fluoro-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1551-(3-methylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1561-[5-(2,5-dimethyl-furan-3-yl-carbonylaminomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1571-(3-chloro-4-isopropylsulfonyl-5-methylthio-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1581-(3,4-dichloro-benzyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1591-thien-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1601-benzo[b]furan-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 161(E)-1-(3-fluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 162(Z)-1-(1-fluoro-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1631-(5,6,7-trihydro-4H-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 164(E)-1-(3-chloro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 165(E)-1-(4-chloro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1661-(3-chloro-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 167(E)-1-(3-trifluoromethoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1681-(4-fluoro-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1691-(5-methylsulfonyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1701-[5-(4-methyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1711-(3-chloro-6-fluoro-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1721-[5-(2,5-dimethyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1731-[5-(2-methoxy-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1741-[5-(2,5-dimethyl-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1751-(3,4-dichloro-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1761-[5-(3,5-difluoro-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1771-(5-naphthalen-1-ylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1781-[5-(4-tert-butyl-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 179(E)-1-(3-methyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 180(E)-1-(4-methyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 181(Z)-1-(1-methyl-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 182(E)-1-(4-fluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 183(Z)-1-(2-methoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 184(E)-1-(3-methoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 185(E)-1-(4-methoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 186(E)-1-(2-chloro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 187(E)-1-(benzodioxol-5-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 188(E)-1-(naphthalen-1-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1891-(1-oxo-2-fluoren-9-ylidene-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 190(E)-1-(1-phenyl-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 191(E)-1-(2-methyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1921-(1-methyl-3H-inden-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1931-(1-methyl-indol-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 194(E)-1-(2-methoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 195(E)-1-(2,6-difluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1961-(2-oxo-(2H)-chromen-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1971-(8-methoxy-(2H)-chromen-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1981-(5-bromo-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 199(E)-1-(2-bromo-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2001-(5-trifluoromethyl-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2011-[3-(4-methoxy-phenyl)-4-cyano-5-methylthio-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2021-[3-(4-chloro-phenyl)-4-cyano-5-methylthio-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2031-(5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2041-thieno[3,2-b]thien-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 205(Z)-1-(1-methylcarbonylamino-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2061-[5-(2-methyl-thiazol-4-yl)-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2071-(3-chloro-6-methyl-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2081-[3-(2-methyl-phenoxy)-benzyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2091-(3-chloro-6-methoxy-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2101-[3-(2-fluoro-phenoxy)-benzyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2111-(3-propylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2121-[5-(2-methoxy-4-propyl-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2131-[5-(2-bromo-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2141-(3-benzylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2151-[1-oxo-2-(3-oxo-3H-isobenzofuran-1-ylidene)-ethyl]-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2161-(5-morpholin-4-ylmethyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2171-(4-phenyl-[1,2,3]thiadiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2181-(3-methylthio-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2191-(3-methylthio-7-hydro-6H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2201-[5-(2-methyl-furan-3-yl-carbonylaminomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2211-[5-(3,5-dimethyl-4-chloro-pyrazol-1-yl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2221-(3-methyl-4-oxo-6-phenyl-5,6,7-trihydro-4H-benzo[b]furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2231-(3-ethylthio-4-oxo-6,6-dimethyl-6,7-dihydro-5H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan],2241-[5-(2-methoxy-4-allyl-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2251-(3-isopropylthio-4-oxo-6,6-dimethyl-6,7-dihydro-5H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan],2261-(3,4-dimethyl-5-cyano-thieno[2,3-b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2271-[5-(3-methoxy-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2281-(3-methyl-6-phenyl-benzo[b]furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2291-(3-butylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2301-(3-chloro-6-bromo-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2311-(3-sec-butylthio-4-oxo-6,6-dimethyl-6,7-dihydro-5H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan],232 1-(3-benzylthio-4-oxo-6,6-dimethyl-6,7-dihydro-5H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan],2331-thieno[2,3-b]thien-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2341-(3-methylthio-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2351-(3-methylthio-4-methoxy-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2361-indol-3-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2371-(1-methyl-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2381-(5-methoxy-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2391-(1-benzyl-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2401-(3-benzylthio-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2411-(3-benzylthio-7-hydro-6H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 242(Z)-1-(furan-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 243(Z)-1-(imidazol-4-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 244(E)-1-(pyridin-4-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2451-(5-formyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2461-(5,6-dihydro-4H-cyclopenta[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2471-(5-methylthio-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 248(E)-1-(1-cyano-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2491-(7-methyl-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2501-(1-ethyl-7-methyl-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 251(E)-1-(furan-3-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 252(E)-1-(pyridin-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 253(E)-1-(pyridin-3-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 254(E)-1-(thien-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 255(E)-1-(thien-3-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2561-(5-dihydroxymethyl-4-methyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2571-(5,6,7,8-tetrahydro-4H-cyclohepta[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2581-(4-cyano-5-methylthio-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2591-(4-methyl-5-bromo-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 260spiro[cyclohexane-1,6′-5,7-dihydro-4H-benzo[b]thiophene]-2′-carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2611-(3-ethoxy-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2621-(3,4-dichlorophenyl)carbonyl-2-oxo-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2631-benzylaminocarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2641-(4-hydroxy-phenylethynyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 265(E)-1-(3-hydroxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2661-(5-tert-butyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2671-(5-methoxycarbonyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 268(E)-1-(4-tert-butyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2691-fluoren-1-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2701-(9-oxo-fluoren-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2711-(3-chloro-6-ethyl-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 272(E)-1-(2-hydroxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2731-(3-aminocarbonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2741-(3-tert-butyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2751-(3,4,5-trichloro-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2761-(4-trifluoromethyl-6-methyl-1H-thieno[2,3-c]pyrazol-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2771-(3-thien-2-yl-[1,2,4]oxadiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2781-(4,5-dibromo-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2791-[4-(3,5-bis-trifluoromethyl-phenoxy)-phenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2801-(3,4-dichlorophenyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 281(E)-1-(3-benzyloxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2821-[5-(4-tert-butyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2831-(1-phenylsulfonyl-1H-indol-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2841-[3-(3-thien-2-yl-[1,2,4]oxadiazol-5-yl)-5-aminocarbonyl-phenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2851-1H-indol-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2861-3H-inden-1-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2871-(3-oxo-indan-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2881-(4-phenyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2891-fluoren-9-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2901-(1-oxo-2,2-diphenyl-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 291(E)-1-[3-(2-methoxy-ethoxy)-phenylethenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2921-9H-xanthen-9-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2931-9H-xanthen-9-ylmethylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 294(E)-1-(3-phenethoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2951-(4-phenyl-5-trifluoromethyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2961-phenylethynylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2971-(5-phenylethynyl-furan-2-yl)carbonyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan]-5′-[methyl-(trimethyl)ammonium], 2981-(1-chloro-naphtho[2,1-b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2991-[3-(4-chloro-phenyl)-5-methylthio-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 300(E)-1-(4-benzyloxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 301(E)-1-[3-(3-methoxy-propoxy)-phenylethenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 302(E)-1-[3-(2-ethoxy-ethoxy)-phenylethenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3031-(3-methyl-4-bromo-5-propoxy-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3041-(5-phenylethynyl-furan-2-yl)carbonyl-5′-formylaminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3051-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminosulfonylaminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3061-(5-phenylethynyl-furan-2-yl)carbonyl-5′-[hydroxyamino(imino)methyl]-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3071-(5-phenylethynyl-furan-2-yl)carbonyl-5′-[hydrazino(imino)methyl]-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3081-(3,4-dichlorophenyl)carbonyl-5′-aminomethyl-6′-fluoro-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 309(E)-1-(2-fluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3101-(5-phenylethynyl-furan-2-yl)carbonyl-5′-[methylamino(imino)methyl]-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3111-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-6′-fluoro-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 312(E)-1-(2,3-difluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3131-(5-phenylethynyl-furan-2-yl)carbonyl-5′-[dimethylamino(imino)methyl]-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3141-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminoethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3151-(3,4-dichlorophenyl)carbonyl-2′-oxo-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3161-(5-phenylethynyl-furan-2-yl)carbonyl-1′-oxo-2′-(2,4-dimethoxy-benzyl)-5′-aminomethyl-spiro[piperidine-4,3′-1H-isoindole], 3171-(5-phenylethynyl-furan-2-yl)carbonyl-1′-oxo-5′-aminomethyl-spiro[piperidine-4,3′-1H-isoindole], 3181-(5-phenylethynyl-furan-2-yl)carbonyl-spiro[piperidine-4,3′-indane],3191-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3201-(5-phenylethynyl-furan-2-yl)carbonyl-1′-ethyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3211-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(2-methoxycarbonyl-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3221-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(2-carboxy-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3231-(5-phenylethynyl-furan-2-yl)carbonyl-1′-methoxycarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3241-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(4-carboxy-phenyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3251-(5-phenylethynyl-furan-2-yl)carbonyl-1′-aminocarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3261-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole]-1′-(2-ethyl-phosphonic acid), 3271-(5-phenylethynyl-furan-2-yl)carbonyl-1′-hydroxysulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3281-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(3-methoxycarbonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3291-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(2-ethoxy-1,2-dioxo-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3301-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(2-1H-tetrazol-5-yl-1-oxo-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3311-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(3-carboxy-phenyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3321-(5-phenylethynyl-furan-2-yl)carbonyl-1′-[4-ethoxy-2-(methylamino)amino-1,4-dioxo-butyl]-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3331-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(methylsulfonylmethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3341-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(1H-tetrazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3351-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(hydroxysulfonylmethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3361-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(1-methyl-imidazol-4-yl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3371-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(5-carboxy-furan-2-yl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3381-(5-phenylethynyl-furan-2-yl)carbonyl-1′-[5-(N′-methyl-hydrazino)-1,1-dioxo-3,4,5-trihydro-(2H)-thien-3-yl]sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3391-(5-phenylethynyl-furan-2-yl)carbonyl-1′-methylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3401-(5-phenylethynyl-furan-2-yl)carbonyl-1′-methylsulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3411-(5-phenylethynyl-furan-2-yl)carbonyl-1′-phenylsulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3421-(5-phenylethynyl-furan-2-yl)carbonyl-1′-aminosulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3431-(5-phenylethynyl-furan-2-yl)carbonyl-1′-[(methoxycarbonyl)methyl]-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3441-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(3-methoxycarbonyl-phenyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3451-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(5-methoxycarbonyl-furan-2-yl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3461-(3-methyl-4-bromo-5-propoxy-thien-2-yl)carbonyl-1′-hydroxysulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3471-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(5-carboxy-thien-3-yl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3481-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(methylsulfonylmethyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3491-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(N′-methylhydrazino-carbonylmethyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole],350 1-(3-methylthio-benzo[c]thien-1-yl)carbonyl-1′-hydroxysulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3511-(4,5-dibromo-thien-2-yl)carbonyl-1′-hydroxysulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3521-(3,4-dichlorophenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(1,1-dioxo-(2H)-benzo[b]thiophene)], 3531-(3,4-dichlorophenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]thiophene], 3541-(2,2-diphenylethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3551-(9H-fluoren-9-ylmethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 356(E)-1-(3-methyl-thien-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3571-[4-(4-chloro-phenyl)-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3581-(5-phenylethynyl-furan-2-yl)carbonyl-1′-thien-2-ylsulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], and 3591-(5-phenylethynyl-furan-2-yl)carbonyl-1′-thien-3-ylsulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole].

A representative compound of Formula (I) or a form thereof includes acompound selected from the group consisting of:

Cpd Name 11-(3,4-dichlorophenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 31-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 41-(3-benzoyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 51-(3-aminothiocarbonylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 71-(9-oxo-10,10-dioxo-thioxanthen-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 121-[5-(4-chloro-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 161-benzothiazol-6-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 171-{4-[(4-benzoxazol-2-yl)-pyrazol-1-yl]-phenyl}carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 191-(3-thien-2-ylmethylcarbonylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 201-(3-benzodioxol-5-yl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 211-[3-(5-chloro-pyrimidin-2-yl)thiophenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 231-[(5-phenylthio)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 241-(3,4-dimethyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 251-(3-methyl-4-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 261-(3,4-difluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 271-(3-chloro-4-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 281-(3-chloro-4-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 291-(3-bromo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 301-(3-methyl-4-bromo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 311-(3-bromo-4-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 321-(3-bromo-4-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 331-(3-nitro-4-bromo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 341-(3-iodo-4-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 351-[5-(2-fluoro-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 361-phenylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan],37 1-cyclohexylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 381-(trans-4-methyl-cyclohexyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 401-(3,4-dimethoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 411-(3-methyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 421-(3-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 431-(4-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 441-(4-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 451-(4-methylthio-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 461-(3-fluoro-4-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 471-(3-trifluoromethyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 481-(3-iodo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 491-(4-iodo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 501-(3-iodo-4-methyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 511-(3-methyl-4-iodo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 521-(3-iodo-4-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 531-(3-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 541-(4-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 561-(3-dimethylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 571-(3-methylthio-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 581-(4-methoxycarbonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 591-(4-bromo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 621-(4-phenoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 631-(3-trifluoromethylthio-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 641-[3-(4-methoxy-phenyl)-phenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 651-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminoiminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 681-benzodioxol-5-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 701-naphthalen-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 711-(4-trifluoromethyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 721-(3-methylsulfonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 741-(3-trifluoromethyl-4-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 751-(4-benzyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 761-(4-benzyloxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 77(Z)-1-(5-phenylethenyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 861-(3,4-dichloro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 881-(3-phenoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 901-(4-fluoro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 911-(4-chloro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 921-(4-phenyl-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 931-(4-bromo-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 941-(4-methoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 961-(4-iodo-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 991-(3-methoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1001-benzodioxol-5-ylmethylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1021-(3-methyl-4-methoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1031-(3-methylthio-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1051-(3,4-dimethoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1061-(3-methoxy-4-benzyloxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1071-(5-phenethyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1081-(phenylethynyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 109(E)-1-(phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1101-benzothien-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 111(E)-1-(3,4-difluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 112(E)-1-(phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 113(E)-1-(naphthalene-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1141-(5-phenyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1151-(3-phenoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 116(E)-1-(3,4-dichloro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 117(E)-1-(4-phenyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1181-(2,4-dimethyl-thiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1201-(5-pyridin-2-yl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1211-(2-pyridin-3-yl-thiazol-4-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1221-(2-pyridin-4-yl-thiazol-4-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1231-(2-phenyl-4-methyl-thiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1261-(6-bromo-naphthalen-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1281-[2-(4-trifluoromethyl-phenyl)-4-methyl-thiazol-5-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1291-[5-(2-chloro-5-trifluoromethyl-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1301-(5-phenyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1311-[5-(4-methyl-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1321-[5-(4-methoxy-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1331-(3,5-di-tert-butyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1341-[5-(3-chloro-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1351-[5-(3-trifluoromethyl-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1361-[5-(2,4-dichloro-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1371-[5-(2,5-dichloro-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1381-[5-(3,4-dichloro-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1391-[5-(3-methyl-4-chloro-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1401-[5-(4-bromo-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1411-(trans-2-phenyl-cyclopropyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1421-(5-phenyl-pyridin-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1431-(5-thien-2-yl-pyridin-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1441-[5-(3-methoxy-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1451-[5-(4-chloro-pyrazol-1-ylmethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1461-[5-(2-chloro-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1471-[5-(benzylthiomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1481-[5-(4,6-dimethyl-pyrimidin-2-ylthiomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1491-[5-(3,5-dichloro-phenoxy)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1501-[5-(3,5-dimethyl-4-bromo-pyrazol-1-yl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1511-[5-(5-trifluoromethyl-pyridin-2-ylthiomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1521-[4-phenylethynyl-pyridin-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1531-[5-(2-methyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1541-[5-(4-fluoro-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1551-(3-methylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1561-[5-(2,5-dimethyl-furan-3-yl-carbonylaminomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1571-(3-chloro-4-isopropylsulfonyl-5-methylthio-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1591-thien-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1601-benzo[b]furan-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 161(E)-1-(3-fluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 162(Z)-1-(1-fluoro-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1631-(5,6,7-trihydro-4H-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 164(E)-1-(3-chloro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 165(E)-1-(4-chloro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1661-(3-chloro-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 167(E)-1-(3-trifluoromethoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1681-(4-fluoro-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1701-[5-(4-methyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1711-(3-chloro-6-fluoro-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1721-[5-(2,5-dimethyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1731-[5-(2-methoxy-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1741-[5-(2,5-dimethyl-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1751-(3,4-dichloro-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1761-[5-(3,5-difluoro-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1771-(5-naphthalen-1-ylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1781-[5-(4-tert-butyl-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 179(E)-1-(3-methyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 180(E)-1-(4-methyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 182(E)-1-(4-fluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 184(E)-1-(3-methoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 186(E)-1-(2-chloro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 187(E)-1-(benzodioxol-5-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 188(E)-1-(naphthalen-1-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1891-(1-oxo-2-fluoren-9-ylidene-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 190(E)-1-(1-phenyl-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 191(E)-1-(2-methyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1921-(1-methyl-3H-inden-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1931-(1-methyl-indol-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 194(E)-1-(2-methoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 195(E)-1-(2,6-difluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1961-(2-oxo-(2H)-chromen-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1971-(8-methoxy-(2H)-chromen-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1981-(5-bromo-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 199(E)-1-(2-bromo-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2011-[3-(4-methoxy-phenyl)-4-cyano-5-methylthio-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2021-[3-(4-chloro-phenyl)-4-cyano-5-methylthio-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2031-(5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2041-thieno[3,2-b]thien-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 205(Z)-1-(1-methylcarbonylamino-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2061-[5-(2-methyl-thiazol-4-yl)-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2081-[3-(2-methyl-phenoxy)-benzyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2101-[3-(2-fluoro-phenoxy)-benzyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2111-(3-propylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2121-[5-(2-methoxy-4-propyl-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2131-[5-(2-bromo-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2141-(3-benzylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2151-[1-oxo-2-(3-oxo-3H-isobenzofuran-1-ylidene)-ethyl]-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2171-(4-phenyl-[1,2,3]thiadiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2181-(3-methylthio-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2191-(3-methylthio-7-hydro-6H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2201-[5-(2-methyl-furan-3-yl-carbonylaminomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2211-[5-(3,5-dimethyl-4-chloro-pyrazol-1-yl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2221-(3-methyl-4-oxo-6-phenyl-5,6,7-trihydro-4H-benzo[b]furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2231-(3-ethylthio-4-oxo-6,6-dimethyl-6,7-dihydro-5H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan],2241-[5-(2-methoxy-4-allyl-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2251-(3-isopropylthio-4-oxo-6,6-dimethyl-6,7-dihydro-5H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan],227 1-[5-(3-methoxy-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2281-(3-methyl-6-phenyl-benzo[b]furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2291-(3-butylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2301-(3-chloro-6-bromo-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2311-(3-sec-butylthio-4-oxo-6,6-dimethyl-6,7-dihydro-5H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan],232 1-(3-benzylthio-4-oxo-6,6-dimethyl-6,7-dihydro-5H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan],2331-thieno[2,3-b]thien-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2341-(3-methylthio-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2351-(3-methylthio-4-methoxy-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2361-indol-3-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2371-(1-methyl-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2381-(5-methoxy-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2391-(1-benzyl-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2401-(3-benzylthio-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2411-(3-benzylthio-7-hydro-6H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 242(Z)-1-(furan-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2451-(5-formyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2461-(5,6-dihydro-4H-cyclopenta[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2471-(5-methylthio-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 248(E)-1-(1-cyano-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2491-(7-methyl-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2501-(1-ethyl-7-methyl-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 254(E)-1-(thien-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 255(E)-1-(thien-3-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2561-(5-dihydroxymethyl-4-methyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2571-(5,6,7,8-tetrahydro-4H-cyclohepta[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2581-(4-cyano-5-methylthio-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2591-(4-methyl-5-bromo-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2611-(3-ethoxy-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 265(E)-1-(3-hydroxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2661-(5-tert-butyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2671-(5-methoxycarbonyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 272(E)-1-(2-hydroxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2751-(3,4,5-trichloro-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2761-(4-trifluoromethyl-6-methyl-1H-thieno[2,3-c]pyrazol-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2771-(3-thien-2-yl-[1,2,4]oxadiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2781-(4,5-dibromo-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2801-(3,4-dichlorophenyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 281(E)-1-(3-benzyloxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2821-[5-(4-tert-butyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2831-(1-phenylsulfonyl-1H-indol-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2841-[3-(3-thien-2-yl-[1,2,4]oxadiazol-5-yl)-5-aminocarbonyl-phenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2851-1H-indol-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2861-3H-inden-1-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2881-(4-phenyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2901-(1-oxo-2,2-diphenyl-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 291(E)-1-[3-(2-methoxy-ethoxy)-phenylethenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 294(E)-1-(3-phenethoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2951-(4-phenyl-5-trifluoromethyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2981-(1-chloro-naphtho[2,1-b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2991-[3-(4-chloro-phenyl)-5-methylthio-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 302(E)-1-[3-(2-ethoxy-ethoxy)-phenylethenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3031-(3-methyl-4-bromo-5-propoxy-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3041-(5-phenylethynyl-furan-2-yl)carbonyl-5′-formylaminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3061-(5-phenylethynyl-furan-2-yl)carbonyl-5′-[hydroxyamino(imino)methyl]-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3071-(5-phenylethynyl-furan-2-yl)carbonyl-5′-[hydrazino(imino)methyl]-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 309(E)-1-(2-fluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3101-(5-phenylethynyl-furan-2-yl)carbonyl-5′-[methylamino(imino)methyl]-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3111-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-6′-fluoro-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 312(E)-1-(2,3-difluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3131-(5-phenylethynyl-furan-2-yl)carbonyl-5′-[dimethylamino(imino)methyl]-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3151-(3,4-dichlorophenyl)carbonyl-2′-oxo-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3161-(5-phenylethynyl-furan-2-yl)carbonyl-1′-oxo-2′-(2,4-dimethoxy-benzyl)-5′-aminomethyl-spiro[piperidine-4,3′-1H-isoindole], 3171-(5-phenylethynyl-furan-2-yl)carbonyl-1′-oxo-5′-aminomethyl-spiro[piperidine-4,3′-1H-isoindole], 3181-(5-phenylethynyl-furan-2-yl)carbonyl-spiro[piperidine-4,3′-indane],3191-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3201-(5-phenylethynyl-furan-2-yl)carbonyl-1′-ethyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3211-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(2-methoxycarbonyl-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3221-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(2-carboxy-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3231-(5-phenylethynyl-furan-2-yl)carbonyl-1′-methoxycarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3241-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(4-carboxy-phenyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3251-(5-phenylethynyl-furan-2-yl)carbonyl-1′-aminocarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3261-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole]-1′-(2-ethyl-phosphonic acid), 3271-(5-phenylethynyl-furan-2-yl)carbonyl-1′-hydroxysulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3281-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(3-methoxycarbonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3291-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(2-ethoxy-1,2-dioxo-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3301-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(2-1H-tetrazol-5-yl-1-oxo-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3311-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(3-carboxy-phenyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3321-(5-phenylethynyl-furan-2-yl)carbonyl-1′-[4-ethoxy-2-(methylamino)amino-1,4-dioxo-butyl]-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3331-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(methylsulfonylmethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3341-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(1H-tetrazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3351-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(hydroxysulfonylmethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3361-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(1-methyl-imidazol-4-yl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3371-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(5-carboxy-furan-2-yl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3381-(5-phenylethynyl-furan-2-yl)carbonyl-1′-[5-(N′-methyl-hydrazino)-1,1-dioxo-3,4,5-trihydro-(2H)-thien-3-yl]sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3391-(5-phenylethynyl-furan-2-yl)carbonyl-1′-methylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3401-(5-phenylethynyl-furan-2-yl)carbonyl-1′-methylsulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3411-(5-phenylethynyl-furan-2-yl)carbonyl-1′-phenylsulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3421-(5-phenylethynyl-furan-2-yl)carbonyl-1′-aminosulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3431-(5-phenylethynyl-furan-2-yl)carbonyl-1′-[(methoxycarbonyl)methyl]-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3441-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(3-methoxycarbonyl-phenyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3451-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(5-methoxycarbonyl-furan-2-yl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3461-(3-methyl-4-bromo-5-propoxy-thien-2-yl)carbonyl-1′-hydroxysulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3471-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(5-carboxy-thien-3-yl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3481-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(methylsulfonylmethyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3491-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(N′-methylhydrazino-carbonylmethyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole],350 1-(3-methylthio-benzo[c]thien-1-yl)carbonyl-1′-hydroxysulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3511-(4,5-dibromo-thien-2-yl)carbonyl-1′-hydroxysulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3531-(3,4-dichlorophenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]thiophene], 3541-(2,2-diphenylethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3551-(9H-fluoren-9-ylmethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 356(E)-1-(3-methyl-thien-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3571-[4-(4-chloro-phenyl)-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3581-(5-phenylethynyl-furan-2-yl)carbonyl-1′-thien-2-ylsulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], and 3591-(5-phenylethynyl-furan-2-yl)carbonyl-1′-thien-3-ylsulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole].

A representative compound of Formula (I) or a form thereof includes acompound selected from the group consisting of:

Cpd Name 3 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 351-[5-(2-fluoro-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 651-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminoiminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1461-[5-(2-chloro-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1521-[4-phenylethynyl-pyridin-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1531-[5-(2-methyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1701-[5-(4-methyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1721-[5-(2,5-dimethyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2141-(3-benzylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)- benzo[b]furan],218 1-(3-methylthio-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2191-(3-methylthio-7-hydro-6H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2291-(3-butylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)- benzo[b]furan],234 1-(3-methylthio-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2351-(3-methylthio-4-methoxy-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2401-(3-benzylthio-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2411-(3-benzylthio-7-hydro-6H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2771-(3-thien-2-yl-[1,2,4]oxadiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 2841-[3-(3-thien-2-yl-[1,2,4]oxadiazol-5-yl)-5-aminocarbonyl-phenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3031-(3-methyl-4-bromo-5-propoxy-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 3171-(5-phenylethynyl-furan-2-yl)carbonyl-1′-oxo-5′-aminomethyl-spiro[piperidine-4,3′-1H-isoindole], 3181-(5-phenylethynyl-furan-2-yl)carbonyl-spiro[piperidine-4,3′- indane],340 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-methylsulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 3411-(5-phenylethynyl-furan-2-yl)carbonyl-1′-phenylsulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], and 3421-(5-phenylethynyl-furan-2-yl)carbonyl-1′-aminosulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole].

CHEMICAL DEFINITIONS & NOMENCLATURE

It should also be noted that any atom with unsatisfied valences in thetext, schemes, examples, structural formulae and any tables herein isassumed to have the hydrogen atom or atoms to satisfy the valences.

As used herein, the following terms are intended to have the followingdefinitions. The definitions herein may specify that a chemical term hasan indicated formula. The particular formula provided is not intended tolimit the scope of the invention, but is provided as an illustration ofthe term. The scope of the per se definition of the term is intended toinclude the plurality of variations expected to be included by one ofordinary skill in the art.

The term “C₁₋₄alkyl” means a saturated branched or straight-chainhydrocarbon radical having from 1 up to 4 carbon atoms in a linear orbranched arrangement. The term includes atom groups such as methyl,ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, tert-butyl and the like. Analkyl radical may be attached to a core molecule by any atom whereallowed by available valences.

The term “C₂₋₄alkenyl” means a saturated branched or straight-chainhydrocarbon radical having from 1 up to 4 carbon atoms in a linear orbranched arrangement and at least one double bond between two adjacentstraight-chain carbon atoms. The term includes atom groups such asethenyl, propenyl, butenyl and the like. An alkenyl radical may beattached to a core molecule by any atom where allowed by availablevalences.

The term “C₂₋₄alkynyl” means a saturated branched or straight-chainhydrocarbon radical having from 1 up to 4 carbon atoms in a linear orbranched arrangement and at least one triple bond between two adjacentstraight-chain carbon atoms. The term includes atom groups such asethynyl, propynyl, butynyl and the like. An alkynyl radical may beattached to a core molecule by any atom where allowed by availablevalences.

The term “C₁₋₄alkoxy” means an alkyl radical having from 1 up to 4carbon atoms in a linear or branched arrangement, as in the formula:—O—C₁₋₄alkyl. The term includes atom groups such as methoxy, ethoxy,propoxy, butoxy and the like. An alkoxy radical may be attached to acore molecule by any atom where allowed by available valences.

The term “C₃₋₁₄cycloalkyl” means a saturated or partially unsaturated,monocyclic, polycyclic or benzofused hydrocarbon ring system radical.The term also includes C₃₋₈cycloalkyl, C₅₋₆cycloalkyl, C₅₋₈cycloalkyland benzofused C₃₋₁₄cycloalkyl ring systems. Examples includecyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexyl,cyclohexenyl, cycloheptyl, cyclooctyl, 1H-indenyl, indanyl,9H-fluorenyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.1]heptanyl and the like.A C₃₋₁₄cycloalkyl radical may be attached to a core molecule by any atomwhere allowed by available valences.

The term “aryl” means an unsaturated, aromatic monocyclic or polycyclichydrocarbon ring system radical. Examples of aryl ring systems includephenyl, naphthalenyl, azulenyl, anthracenyl and the like. An arylradical may be attached to a core molecule by any atom where allowed byavailable valences.

The term “hetero”, when used as a prefix for a ring system, refers tothe replacement of at least one carbon atom member in the ring systemwith a heteroatom selected from N, O, S, S(O), or SO₂. A hetero ring mayhave 1, 2, 3 or 4 carbon atom members replaced by a nitrogen atom.Alternatively, a ring may have 1, 2 or 3 nitrogen atom members and 1oxygen or sulfur atom member. Alternatively, a ring may have 1 oxygen orsulfur atom member. Alternatively, up to two adjacent ring members maybe heteroatoms, wherein one heteroatom is nitrogen and the otherheteroatom is selected from N, S or O.

The term “heterocyclyl” means a saturated or partially unsaturated,monocyclic or polycyclic “hetero” ring system radical. Heterocyclyl ringsystems include 2H-pyrrole, 2-pyrrolinyl, 3-pyrrolinyl, pyrrolidinyl,1,3-dioxolanyl, 2-imidazolinyl (also referred to as4,5-dihydro-1H-imidazolyl), imidazolidinyl, 2-pyrazolinyl,pyrazolidinyl, tetrazolyl, tetrazolidinyl, piperidinyl, 1,4-dioxanyl,morpholinyl, 1,4-dithianyl, thiomorpholinyl, piperazinyl, azetidinyl,azepanyl, hexahydro-1,4-diazepinyl, hexahydro-1,4-oxazepanyl,tetrahydro-furanyl, tetrahydro-thienyl, tetrahydro-pyranyl,tetrahydro-pyridazinyl, 2,5-diaza-bicyclo[2.2.1]heptanyl,2-oxa-5-aza-bicyclo[2.2.1]heptanyl and the like. A heterocyclyl radicalmay be attached to a core molecule by any atom where allowed byavailable valences.

The term “heterocyclyl” also includes a benzofused-heterocyclyl ringsystem radical. The term “benzofused-heterocyclyl” means a heterocyclylring system radical having a benzene ring fused on the ring system onadjacent carbons, such as indolinyl (also referred to as2,3-dihydro-indolyl), benzo[1,3]dioxolyl, 2,3-dihydro-1,4-benzodioxinyl,2,3-dihydro-benzofuranyl, 1,2-dihydro-phthalazinyl and the like. Abenzofused-heterocyclyl radical may be attached to a core molecule byany atom where allowed by available valences.

The term “heteroaryl” means an unsaturated monocyclic, polycyclicaromatic “hetero” ring system radical. Heteroaryl ring systems includefuryl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl,isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl and the like. Aheteroaryl radical may be attached to a core molecule by any atom whereallowed by available valences.

The term “heteroaryl” also includes a benzofused-heteroaryl ring systemradical. The term “benzofused-heteroaryl” means a heteroaryl ring systemradical having a benzene ring fused on the ring system on adjacentcarbons, such as indolizinyl, indolyl, azaindolyl, isoindolyl,benzofuranyl, benzothienyl, indazolyl, azaindazolyl, benzoimidazolyl,benzothiazolyl, benzoxazolyl, benzoisoxazolyl, benzothiadiazolyl,benzotriazolyl, purinyl, 4H-quinolizinyl, quinolinyl, isoquinolinyl,cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl,1,8-naphthyridinyl, pteridinyl and the like. A benzofused-heteroarylradical may be attached to a core molecule by any atom where whenallowed by available valences.

The term “C₁₋₄alkoxyC₁₋₄alkoxy” means a radical of the formula:—O—C₁₋₄alkyl-O—C₁₋₄alkyl.

The term “C₁₋₄alkoxyC₁₋₄alkyl” means a radical of the formula:—C₁₋₄alkyl-O—C₁₋₄alkyl.

The term “C₁₋₄alkoxycarbonyl” means a radical of the formula:—C(O)—O—C₁₋₄alkyl.

The term “C₁₋₄alkoxycarbonylC₁₋₄alkyl” means a radical of the formula:—C₁₋₄alkyl-C(O)—O—C₁₋₄alkyl.

The term “C₁₋₄alkoxycarbonylC₁₋₄alkylcarbonyl” means a radical of theformula: —C(O)—C₁₋₄alkyl-C(O)—O—C₁₋₄alkyl.

The term “C₁₋₄alkoxycarbonylC₁₋₄alkylsulfonyl” means a radical of theformula: —SO₂—C₁₋₄alkyl-C(O)—O—C₁₋₄alkyl.

The term “C₁₋₄alkoxycarbonylcarbonyl” means a radical of the formula:—C(O)—C(O)—O—C₁₋₄alkyl.

The term“(C₁₋₄alkyl)aminoamino” means a radical of the formula:—NH—NH—C₁₋₄alkyl

The term “C₁₋₄alkylcarbonyl” means a radical of the formula:—C(O)—C₁₋₄alkyl.

The term “C₁₋₄alkylcarbonylamino” means a radical of the formula:—NH—C(O)—C₁₋₄alkyl.

The term “C₁₋₄alkylsulfonyl” means a radical of the formula:—SO₂—C₁₋₄alkyl.

The term “C₁₋₄alkylsulfonylC₁₋₄alkylcarbonyl” means a radical of theformula: —C(O)—C₁₋₄alkyl-SO₂—C₁₋₄alkyl.

The term “C₁₋₄alkylsulfonylC₁₋₄alkylsulfonyl” means a radical of theformula: —SO₂—C₁₋₄alkyl-SO₂—C₁₋₄alkyl.

The term “C₁₋₄alkylthio” means a radical of the formula: —S—C₁₋₄alkyl.

The terms “amino,” “(C₁₋₄alkyl)amino” and “(C₁₋₄alkyl)₂-amino” mean aradical of the formula: —NH₂, —NH—C₁₋₄alkyl and —N(C₁₋₄alkyl)₂,respectively.

The terms “aminoC₁₋₄alkyl,” “(C₁₋₄alkyl)aminoC₁₋₄alkyl,”“(C₁₋₄alkyl)₂-aminoC₁₋₄alkyl” and “(C₁₋₄alkyl)₃-aminoC₁₋₄alkyl” mean aradical of the formula: —C₁₋₄alkyl-NH₂, —C₁₋₄alkyl-NH—C₁₋₄alkyl,—C₁₋₄alkyl-N(C₁₋₄alkyl)₂ and —C₁₋₄alkyl-N⁺(C₁₋₄alkyl)₃, respectively.

The term “aminocarbonyl” means a radical of the formula: —C(O)—NH₂.

The terms “aminoimino,” “hydroxyaminoimino,” “(C₁₋₄alkyl)aminoimino,”“(C₁₋₄alkyl)₂-aminoimino” and “aminoaminoimino” mean a radical of theformula: —C(NH)—NH₂, —C(NH)—NHOH, —C(NH)—N(C₁₋₄alkyl),—C(NH)—N(C₁₋₄alkyl)₂ and —C(NH)—NH—NH₂, respectively.

The terms “aminosulfonyl,” “(C₁₋₄alkyl)aminosulfonyl” and“(C₁₋₄alkyl)₂-aminosulfonyl” mean a radical of the formula: —SO₂—NH₂,—SO₂—NH—C₁₋₄alkyl and —SO₂—N(C₁₋₄alkyl)₂, respectively.

The term “aminosulfonylaminoC₁₋₄alkyl” means a radical of the formula:—C₁₋₄alkyl-NH—SO₂—NH₂.

The term “aminothiocarbonylamino” means a radical of the formula:—NH—C(S)—NH₂.

The term “arylC₁₋₄alkoxy” means a radical of the formula:—O—C₁₋₄alkyl-aryl

The terms “arylC₁₋₄alkyl” and “(aryl)₁₋₂C₁₋₄alkyl” mean a radical of theformula: —C₁₋₄alkyl-aryl and —C₁₋₄alkyl-(aryl)₁₋₂, respectively, whereinC₁₋₄alkyl is substituted on one or more available carbon chain atomswith one or more aryl radicals when allowed by available valences or asindicated by a subscript integer.

The term “arylC₁₋₄alkylamino” means a radical of the formula:—NH—C₁₋₄alkyl-aryl.

The term “arylC₁₋₄alkylaminoC₁₋₄alkyl” means a radical of the formula:—C₁₋₄alkyl-NH—C₁₋₄alkyl-aryl.

The term “arylC₁₋₄alkylcarbonylaminoC₁₋₄alkyl” means a radical of theformula: —C₁₋₄alkyl-NH—C(O)—C₁₋₄alkyl-aryl.

The term “arylC₁₋₄alkylthio” means a radical of the formula:—S—C₁₋₄alkyl-aryl.

The term “arylC₁₋₄alkylthioC₁₋₄alkyl” means a radical of the formula:—C₁₋₄alkyl-S—C₁₋₄alkyl-aryl.

The term “arylC₂₋₄alkenyl” means a radical of the formula:—C₂₋₄alkenyl-aryl.

The term “arylC₂₋₄alkenylcarbonylaminoC₁₋₄alkyl” means a radical of theformula: —C₁₋₄alkyl-NH—C(O)—C₂₋₄alkenyl-aryl.

The term “arylC₂₋₄alkynyl” means a radical of the formula:—C₂₋₄alkynyl-aryl.

The term “arylC₂₋₄alkynylcarbonylaminoC₁₋₄alkyl” means a radical of theformula: —C₁₋₄alkyl-NH—C(O)—C₂₋₄alkynyl-aryl.

The term “arylcarbonyl” means a radical of the formula: —C(O)-aryl.

The term “arylcarbonylaminoC₁₋₄alkyl” means a radical of the formula:—C₁₋₄alkyl-NH—C(O)-aryl.

The term “aryloxy” means a radical of the formula: —O-aryl

The term “aryloxyC₁₋₄alkyl” means a radical of the formula:—C₁₋₄alkyl-O-aryl

The term “arylsulfonyl” means a radical of the formula: —SO₂-aryl.

The term “arylsulfonylamino” means a radical of the formula:—NH—SO₂-aryl.

The term “arylsulfonylaminoC₁₋₄alkyl” means a radical of the formula:—C₁₋₄alkyl-NH—SO₂-aryl.

The term “arylthio” means a radical of the formula: —S-aryl

The term “carbonyl” means a radical of the formula: —C(O)—.

The term “carboxy” means a radical of the formula: —C(O)OH.

The term “carboxyC₁₋₄alkyl” means a radical of the formula:—C₁₋₄alkyl-C(O)OH.

The term “C₃₋₁₄cycloalkylC₁₋₄alkyl” means a radical of the formula:—C₁₋₄alkyl-C₃₋₁₄cycloalkyl.

The term “C₃₋₁₄cycloalkylcarbonylaminoC₁₋₄alkyl” means a radical of theformula: —C₁₋₄alkyl-NH—C(O)—C₃₋₁₄cycloalkyl.

The term “C₃₋₁₄cycloalkylC₁₋₄alkenyl” means a radical of the formula:—C₁₋₄alkyl-NH—C(O)-methenylene-C₃₋₁₄cycloalkyl and—C₁₋₄alkyl-NH—C(O)—C₂₋₄alkenyl-C₃₋₁₄cycloalkyl.

The term “C₃₋₁₄cycloalkylC₂₋₄alkenylcarbonylaminoC₁₋₄alkyl” means aradical of the formula: —C₁₋₄alkyl-NH—C(O)—C₂₋₄alkenyl-C₃₋₁₄cycloalkyl.

The term “formyl” means a radical of the formula: —C(O)H.

The term “formylaminoC₁₋₄alkyl” means a radical of the formula:—C₁₋₄alkyl-NH—C(O)H.

The term “halogen” or “halo” means the group chloro, bromo, fluoro oriodo.

The terms “haloC₁₋₄alkoxy,” “haloC₁₋₄alkyl” and “haloC₁₋₄alkylthio” meana radical of the formula: —O—C₁₋₄alkyl-halo, —C₁₋₄alkyl-halo and—S—C₁₋₄alkyl-halo, respectively, wherein C₁₋₄alkyl is substituted on oneor more available carbon atoms with one or more halo atoms when allowedby available valences.

The term “heteroarylC₁₋₄alkyl” means a radical of the formula:—C₁₋₄alkyl-heteroaryl.

The term “heteroarylC₁₋₄alkylcarbonyl” means a radical of the formula:—C(O)—C₁₋₄alkyl-heteroaryl.

The term “heteroarylC₁₋₄alkylcarbonylamino” means a radical of theformula: —NH—C(O)—C₁₋₄alkyl-heteroaryl.

The term “heteroarylC₂₋₄alkenyl” means a radical of the formula:—C₂₋₄alkenyl-heteroaryl.

The term “heteroarylC₂₋₄alkenylcarbonylaminoC₁₋₄alkyl” means a radicalof the formula: —C₁₋₄alkyl-NH—C(O)—C₂₋₄alkenyl-heteroaryl.

The term “heteroarylcarbonyl” means a radical of the formula:—C(O)-heteroaryl.

The term “heteroarylcarbonylaminoC₁₋₄alkyl” means a radical of theformula: —C₁₋₄alkyl-NH—C(O)-heteroaryl.

The term “heteroarylsulfonyl” means a radical of the formula:—SO₂-heteroaryl.

The term “heteroarylthio” means a radical of the formula: —S-heteroaryl.

The term “heteroarylthioC₁₋₄alkyl” means a radical of the formula:—C₁₋₄alkyl-S-heteroaryl.

The term “heterocyclylcarbonylaminoC₁₋₄alkyl” means a radical of theformula: —C₁₋₄alkyl-NH—C(O)-heterocyclyl.

The term “heteroaryl-heteroaryl” means a radical of the formula:-heteroaryl-heteroaryl, wherein a heteroaryl ring is substituted on anavailable carbon atom with a second heteroaryl ring.

The term “heterocyclylC₁₋₄alkyl” means a radical of the formula:—C₁₋₄alkyl-heterocyclyl.

The term “heterocyclylC₁₋₄alkylcarbonylaminoC₁₋₄alkyl” means a radicalof the formula: —C₁₋₄alkyl-NH—C(O)—C₁₋₄alkyl-heterocyclyl.

The term “heterocyclylC₁₋₄alkenyl” means a radical of the formula:-methenylene-heterocyclyl and —C₂₋₄alkenyl-heterocyclyl.

The term “heterocyclylC₁₋₄alkenylcarbonylaminoC₁₋₄alkyl” means a radicalof the formula: —C₁₋₄alkyl-NH—C(O)-methenylene-heterocyclyl and—C₁₋₄alkyl-NH—C(O)—C₂₋₄alkenyl-heterocyclyl.

The term “heterocyclylcarbonyl” means a radical of the formula:—C(O)-heterocyclyl.

The term “heterocyclylsulfonyl” means a radical of the formula:—SO₂-heterocyclyl.

The term “hydroxyC₁₋₄alkyl” means a radical of the formula:—C₁₋₄alkyl-hydroxy, wherein C₁₋₄alkyl is substituted on one or moreavailable carbon atoms with one or more hydroxy groups when allowed byavailable valences.

The term “hydroxysulfonyl” means a radical of the formula: —SO₂—OH.

The term “hydroxysulfonylC₁₋₄alkylcarbonyl” means a radical of theformula: —C(O)—C₁₋₄alkyl-SO₂—OH.

The term “nitro” means a radical of the formula: —NO₂.

The term “oxo” means a radical of the formula: ═O.

The term “P[(O)(OH)₂]-C₁₋₄alkyl” means a radical of the formula:—C₁₋₄alkyl-{P[(O)(OH)_(2]}.)

The term “sulfonyl” means a radical of the formula: —SO₂—.

The term “substituted” means the independent replacement of one or morehydrogen atoms within a radical with that amount of substituents allowedby available valences.

The term “each instance” means that substitution may occur on a variablewhen the variable is referred to in any configuration. For example, theterm “wherein each instance of heteroaryl is substituted” means thatsubstitution may occur as indicated on the heteroaryl ring in eachinstance heteroaryl is referred to in a heteroaryl, (heteroaryl)aryl or(heteroaryl)heteroaryl substituent. When the term “each instance” is notused, substitution may occur only on the variable referred to.

The term “each selected from” means that, for a variable having multiplesubstituents, each substituent may be independently selected from theindicated group.

In general, IUPAC nomenclature rules are used herein.

Compound Forms

The term “about,” whether used explicitly or not in reference to aquantitative expression given herein, means that every quantity givenherein qualified with the term or otherwise is meant to refer both tothe actual given value and the approximation to such given value thatwould reasonably be inferred based on the ordinary skill in the art,including approximations due to experimental and/or measurementconditions for such given value.

The term “form” means, in reference to compounds of the presentinvention, such may exist as, without limitation, a salt, stereoisomer,tautomer, crystalline, polymorph, amorphous, solvate, hydrate, ester,prodrug or metabolite form. The present invention encompasses all suchcompound forms and mixtures thereof.

The term “isolated form” means, in reference to compounds of the presentinvention, such may exist in an essentially pure state such as, withoutlimitation, an enantiomer, a racemic mixture, a geometric isomer (suchas a cis or trans stereoisomer), a mixture of geometric isomers, and thelike. The present invention encompasses all such compound forms andmixtures thereof.

The compounds of the present invention may also be present in the formof pharmaceutically acceptable salts. For use in medicine, the salts ofthe compounds of this invention refer to non-toxic “pharmaceuticallyacceptable salts” (Ref. International J. Pharm., 1986, 33, 201-217; J.Pharm. Sci., 1997 (January), 66, 1, 1). Other salts well known to thosein the art may, however, be useful in the preparation of compoundsaccording to this invention or of their pharmaceutically acceptablesalts. Representative organic or inorganic acids include, but are notlimited to, hydrochloric, hydrobromic, hydriodic, perchloric, sulfuric,nitric, phosphoric, acetic, propionic, glycolic, lactic, succinic,maleic, fumaric, malic, tartaric, citric, benzoic, mandelic,methanesulfonic, hydroxyethanesulfonic, benzenesulfonic, oxalic, pamoic,2-naphthalenesulfonic, p-toluenesulfonic, cyclohexanesulfamic,salicylic, saccharinic or trifluoroacetic acid. Representative organicor inorganic bases include, but are not limited to, basic or cationicsalts such as benzathine, chloroprocaine, choline, diethanolamine,ethylenediamine, meglumine, procaine, aluminum, calcium, lithium,magnesium, potassium, sodium and zinc.

The present invention includes within its scope prodrugs of thecompounds of this invention. In general, such prodrugs will befunctional derivatives of the compounds that are readily convertible invivo into the required compound. Thus, in the methods of treatment ofthe present invention, the term “administering” shall encompass thetreatment of the various disorders described with the compoundspecifically disclosed or with a compound which may not be specificallydisclosed, but which converts to the specified compound in vivo afteradministration to the patient. Conventional procedures for the selectionand preparation of suitable prodrug derivatives are described, forexample, in “Design of Prodrugs”, ed. H. Bundgaard, Elsevier, 1985.

Where the compounds according to this invention have at least one chiralcenter, they may accordingly exist as enantiomers. Where the compoundspossess two or more chiral centers, they may additionally exist asdiastereomers. It is to be understood that all such isomers and mixturesthereof are encompassed within the scope of the present invention.Furthermore, some of the crystalline forms for the compounds may existas polymorphs and as such are intended to be included in the presentinvention. In addition, some of the compounds may form solvates withwater (i.e., hydrates) or common organic solvents, and such solvates arealso intended to be encompassed within the scope of this invention.

Where the processes for the preparation of the compounds according tothe invention give rise to mixture of stereoisomers, these isomers maybe separated by conventional techniques such as preparativechromatography. The compounds may be prepared in racemic form, orindividual enantiomers may be prepared either by enantiospecificsynthesis or by resolution. The compounds may, for example, be resolvedinto their component enantiomers by standard techniques, such as theformation of diastereomeric pairs by salt formation with an opticallyactive acid, such as (−)-di-p-toluoyl-d-tartaric acid and/or(+)-di-p-toluoyl-l-tartaric acid followed by fractional crystallizationand regeneration of the free base. The compounds may also be resolved byformation of diastereomeric esters or amides, followed bychromatographic separation and removal of the chiral auxiliary.Alternatively, the compounds may be resolved using a chiral HPLC column.

During any of the processes for preparation of the compounds of thepresent invention, it may be necessary and/or desirable to protectsensitive or reactive groups on any of the molecules concerned. This maybe achieved by means of conventional protecting groups, such as thosedescribed in Protective Groups in Organic Chemistry, ed. J. F. W.McOmie, Plenum Press, 1973; and T. W. Greene & P. G. M. Wuts, ProtectiveGroups in Organic Synthesis, John Wiley & Sons, 1991. The protectinggroups may be removed at a convenient subsequent stage using methodsknown from the art.

Therapeutic Use

The compounds of Formula (I) are useful for treating inflammatorydisorders such as immunomediated inflammatory disorders and mast cellmediated inflammatory disorders. Examples of immunomediated inflammatorydisorders for which the compounds of the present invention are usefulinclude, but are not limited to, asthma, allergic rhinitis, rheumatoidarthritis, rheumatoid spondylitis, osteoarthritis, gouty arthritis,arthritic conditions in general (i.e., arthritis), peptic ulcers, ocularand vernal conjunctivitis, inflammatory bowel disease, chronicobstructive pulmonary disease (“COPD”; see Grashoff, W. F. et al.,American Journal of Pathology, 151(6):1785-90, December 1997), Crohn'sdisease, urticaria, bullous pemphiguoid, schleroderma, fibrosis,dermatitis, psoriasis, angioedema, eczematous dermatitis, anaphylaxis,hyperproliferative skin disease, inflammatory skin conditions, hepaticcirrhosis, glomerulonephritis, nephritis, vascular inflammation,atherosclerosis or restenosis.

The compounds of Formula (I) have also been shown to be effective incausing skin depigmentation and therefore may be useful in the treatmentand/or prevention of skin hyperpigmentation.

The compounds of Formula (I) also function as inhibitors of thrombin andfactor Xa. Consequently, they may be useful for the treatment ofthrombin and/or factor Xa mediated disorders, such as thrombosis.

Therapeutic agents that may be useful for administration in combinationwith compounds of Formula (I) include β-adrenergic agonists (e.g.albuterol, terbutaline, formoterol, fenoterol, prenaline and the like)methylxanthines (e.g. caffeine, theophylline, aminophylline,theobromine, and the like) and corticosteroids (e.g. beclomethasome,triamcinolone, flurisolide, dexamethasone, hydrocortisone, prednisoneand the like). In general, one of ordinary skill in the art, acting inreliance upon personal knowledge and the disclosure of this application,will be able to ascertain the amounts of these respective therapeuticagents and the amount of the compound of Formula (I) which should beadministered to a subject to treat a given immunomediated inflammatorydisease.

The present invention is directed to a method for treating a tryptasemediated inflammatory, vascular or dermatological condition in a subjectin need thereof comprising administering to the subject an effectiveamount of a compound of Formula (I).

The tryptase mediated inflammatory, vascular or dermatological conditionis selected from, but not limited to, inflammatory diseases associatedwith the respiratory tract, such as asthma and allergic rhinitis, aswell as other immunomediated inflammatory disorders, such as rheumatoidarthritis, rheumatoid spondylitis, osteoarthritis, gouty arthritis,peptic ulcers, ocular and vernal conjunctivitis, psoriasis, inflammatorybowel disease, Crohn's disease, chronic obstructive pulmonary disease,urticaria, bullous pemphiguoid, schleroderma, fibrosis, dermatitis,psoriasis, pruritis, angioedema, eczematous dermatitis, anaphylaxis,hyperproliferative skin disease, inflammatory skin conditions, hepaticcirrhosis, glomerulonephritis, nephritis, vascular inflammation,atherosclerosis or restenosis.

The tryptase mediated inflammatory, vascular or dermatological conditionis further selected from asthma, allergic rhinitis, inflammatory boweldisease, Crohn's disease or pruritis.

The present invention includes the use of any of the compounds ofFormula (I) for the preparation of a medicament for treating a tryptasemediated inflammatory, vascular or dermatological condition in a subjectin need thereof.

The term “administering” with respect to the methods of the presentinvention, refers to a means for treating, ameliorating or preventing adisease as described herein with a compound specifically disclosed or acompound or prodrug thereof, which would obviously be included withinthe scope of the invention albeit not specifically disclosed for certainof the instant compounds.

Such methods include administering an effective amount of one or morecompounds of Formula (I) or a form, composition or medicament thereof atdifferent times during the course of a therapy or concurrently in acombination form. Such methods further include administering aneffective amount of one or more compounds of Formula (I) or a form,composition or medicament thereof with one or more agents at differenttimes during the course of a therapy or concurrently in a combinationform.

The term “prodrug” refers to a metabolic precursor of a compound ofFormula (I) or a form thereof. In general, a prodrug is a functionalderivative of a compound which may be inactive when administered to apatient but is readily convertible in vivo into an active metabolitecompound.

The term “active metabolite” refers to a metabolic product of a compoundthat is effective for ameliorating, treating or preventing a thrombinmediated disease, disorder or condition. Conventional procedures for theselection and preparation of suitable prodrug derivatives are described,for example, in “Design of Prodrugs”, ed. H. Bundgaard, Elsevier, 1985.

The term “patient” as used herein, refers to an animal, preferably amammal, most preferably a human, who has been the object of treatment,observation or experiment and is at risk of (or susceptible to)developing a disease or having a disease related to unregulated kinaseactivity.

The term “effective amount” refers to that amount of active compound orpharmaceutical agent that elicits the biological or medicinal response(such as inhibiting unregulated kinase activity) in a patient's tissuesystem, animal or human, that is being sought by a researcher,veterinarian, medical doctor, or other clinician.

The effective amount of a compound of Formula (I) exemplified in such amethod is from about 0.001 mg/kg/day to about 300 mg/kg/day.

The term “composition” refers to a product containing one or morecompounds of Formula (I) or a form thereof (such as a product comprisingthe specified ingredients in the specified amounts, as well as anyproduct which results, directly or indirectly, from such combinations ofthe specified ingredients in the specified amounts).

The term “medicament” refers to one or more compounds of Formula (I) ora form thereof used in manufacturing a product for use in ameliorating,treating or preventing a thrombin mediated disease, disorder orcondition.

A formulation of a composition or medicament of the present invention is“pharmaceutically acceptable” when the molecular entities and componentsused therein are of sufficient purity and quality such that, whenappropriately administered to an animal or a human, the formulation doesnot produce an adverse, allergic or other untoward reaction. Since bothhuman use (clinical and over-the-counter) and veterinary use are equallyincluded within the scope of the present invention, a pharmaceuticallyacceptable formulation would include a composition or medicament foreither human or veterinary use.

Even though the compounds of the present invention (including theirpharmaceutically, acceptable salts and pharmaceutically acceptablesolvates) can be administered alone, they will generally be administeredin admixture with a pharmaceutical carrier, excipient or diluentselected with regard to the intended route of administration andstandard pharmaceutical or veterinary practice. Thus, the presentinvention is directed to pharmaceutical and veterinary compositionscomprising compounds of Formula (I) and one or more pharmaceuticallyacceptable carriers, excipients or diluents.

By way of example, in the pharmaceutical and veterinary compositions ofthe present invention, the compounds of the present invention may beadmixed with any suitable binder(s), lubricant(s), suspending agent(s),coating agent(s), and/or solubilising agent(s).

Tablets or capsules of the compounds may be administered singly or twoor more at a time, as appropriate. It is also possible to administer thecompounds in sustained release formulations.

For some applications, the compositions are administered orally in theform of tablets containing excipients such as starch or lactose, or incapsules or ovules either alone or in admixture with excipients, or inthe form of elixirs, solutions or suspensions containing flavoring orcoloring agents.

The compositions (as well as the compounds alone) can also be injectedparenterally, for example intracavernosally, intravenously,intramuscularly or subcutaneously. In this case, the compositions willcomprise a suitable carrier or diluent.

For parenteral administration, the compositions are best used in theform of a sterile aqueous solution which may contain other substances,for example enough salts or monosaccharides to make the solutionisotonic with blood.

For buccal or sublingual administration the compositions may beadministered in the form of tablets or lozenges which can be formulatedin a conventional manner.

Alternatively, the compounds of the general Formula (I) can beadministered by inhalation or in the form of a suppository or pessary,or they may be applied topically in the form of a lotion, solution,cream, ointment or dusting powder. An alternative means of transdermaladministration is by use of a skin patch. For example, they can beincorporated into a cream consisting of an aqueous emulsion ofpolyethylene glycols or liquid paraffin. They can also be incorporated,at a concentration of between 1 and 10% by weight, into an ointmentconsisting of a white wax or white soft paraffin base together with suchstabilizers and preservatives as may be required.

By way of further example, pharmaceutical and veterinary compositionscontaining one or more of the compounds of the invention describedherein as the active ingredient can be prepared by intimately mixing thecompound or compounds with a pharmaceutical carrier according toconventional pharmaceutical compounding techniques. The carrier may takea wide variety of forms depending upon the desired route ofadministration (e.g., oral, parenteral). Thus for liquid oralpreparations such as suspensions, elixirs and solutions, suitablecarriers and additives include water, glycols, oils, alcohols, flavoringagents, preservatives, stabilizers, coloring agents and the like; forsolid oral preparations, such as powders, capsules and tablets, suitablecarriers and additives include starches, sugars, diluents, granulatingagents, lubricants, binders, disintegrating agents and the like. Solidoral preparations may also be coated with substances such as sugars orbe enteric-coated so as to modulate the major site of absorption. Forparenteral administration, the carrier will usually consist of sterilewater and other ingredients may be added to increase solubility orpreservation. Injectable suspensions or solutions may also be preparedutilizing aqueous carriers along with appropriate additives.

Advantageously, compounds of the present invention may be administeredin a single daily dose, or the total daily dosage may be administered individed doses of two, three or four times daily. Furthermore, compoundsfor the present invention can be administered in intranasal form viatopical use of suitable intranasal vehicles, or via transdermal skinpatches well known to those skilled in that art. To be administered inthe form of a transdermal delivery system, the dosage administrationwill, of course, be continuous rather than intermittent throughout thedosage regimen.

It is also apparent to one skilled in the art that the therapeuticallyeffective dose for active compounds of the invention or a pharmaceuticalcomposition thereof will vary according to the desired effect.Therefore, optimal dosages to be administered may be readily determinedand will vary with the particular compound used, the mode ofadministration, the strength of the preparation, and the advancement ofthe disease condition. In addition, factors associated with theparticular subject being treated, including subject age, weight, dietand time of administration, will result in the need to adjust the doseto an appropriate therapeutic level. The above dosages are thusexemplary of the average case. There can, of course, be individualinstances where higher or lower dosage ranges are merited, and such arewithin the scope of this invention.

Compounds of this invention may be administered in any of the foregoingcompositions and dosage regimens or by means of those compositions anddosage regimens established in the art whenever use of the compounds ofthe invention as tryptase inhibitors is required for a subject in needthereof.

The invention also provides a pharmaceutical or veterinary pack or kitcomprising one or more containers filled with one or more of theingredients of the pharmaceutical and veterinary compositions of theinvention. Optionally associated with such container(s) can be a noticein the form prescribed by a governmental agency regulating themanufacture, use or sale of pharmaceuticals or biological products,which notice reflects approval by the agency of manufacture, use or salefor human administration.

Optimal dosages of the compounds of Formula (I) to be administered fortreating a tryptase mediated inflammatory, vascular or dermatologicalcondition may be readily determined by those skilled in the art, andwill vary with the particular compound used, the strength of thepreparation, the mode of administration, and the advancement of thecondition. In addition, factors associated with the particular patientbeing treated, including patient age, weight, diet and time ofadministration, will result in the need to adjust dosages.

General Synthetic Methods

Compounds of the present invention may be prepared by the application oradaptation of known methods, meaning methods used heretofore ordescribed in the literature. Examples of such methods are described byR. C. Larock in Comprehensive Organic Transformations, 2^(nd) ed., JohnWiley & Sons Ltd publishers (1999) and in Comprehensive OrganicSynthesis, Volumes 1-9, Barry M. Trost, Ed., Pergamon Press publishers(1991).

In the reactions used to prepared compounds of the present invention, itmay be necessary to protect reactive functional groups, for example,amino groups, in order to avoid their unwanted participation in thereactions. Conventional protecting groups may be used in accordance withstandard practice, such as those described by T. W. Greene and P. G. M.Wuts in Protective Groups in Organic Chemistry, 3^(rd) ed., John Wileyand Sons Ltd publishers (1999).

The compounds of the present invention may be prepared more particularlyin accordance with the general synthetic schemes described below. Sinceeach scheme is an illustration, the invention should not be construed asbeing limited by the particular chemical reactions depicted or thespecific reagents, protecting groups, solvents and reaction conditionsexpressed. The preparation of the various starting materials used in theschemes is well within the skill of persons versed in the art.

Abbreviations used the following sections are listed in the table below.

Abbreviation Meaning ACE-Cl α-chloroethyl chloroformate ACN AcetonitrileAIBN 2,2′-azobis(2-methylpropionitrile) (+/−)-BINAP(+/−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene Boctert-butyloxycarbonyl BOPbenzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateBOP-Cl bis(2-oxo-3-oxazolidinyl)phosphinic chloride, CAS# ChemicalAbstracts Service Registry Number Cbz benzyloxycarbonyl Cpd compound DBU1,8-diazabicyclo[5.4.0]undec-7-ene DCC dicyclohexylcarbodiimide DCEdichloroethane DCM dichloromethane DIBAL diisobutylaluminum hydride DICN,N′-dicyclohexylcarbodiimide DIPEA N,N-diisopropylethylamine DMAPdimethylaminopyridine DMF N,N-dimethylformamide DMSO dimethyl sulfoxideEDC 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride ESIelectrospray ionization Et₃N or TEA triethylamine EtOAc ethyl acetateFmoc 9-fluorenylmethyloxycarbonyl h/hr/hrs hour(s) HCl hydrogen chlorideHOAc glacial acetic acid HOBT 1-hydroxybenzotriazole hydrate HBTUO-benzotriazol-1-yloxy-N,N,N′,N′-tetramethyluronium hexafluorophosphateLiOH lithium hydroxide min minute(s) MS mass spectroscopy Mtr4-methoxy-2,3,6-trimethylbenzenesufonyl NMR nuclear magnetic resonancespectroscopy PG protecting group ov overlapping Pht phthaloyl PMBpara-methoxylbenzyl PyBrOP bromotris(pyrrolidino)phosphoniumhexafluorophosphate, RT/rt room temperature TEA triethylamine Teoc[2-(trimethylsilyl)ethoxy]carbonyl TFA trifluoroacetic acid THFtetrahydrofuran TLC thin layer chromatography TMS trimethylsilyl Tosp-toluenesulfonyl

Scheme A describes the solution-phase synthesis of certain5-aminomethyl-spiro[benzofuran-3(2H), 4′-piperidine] derivatives A9 ofFormula (I).

Scheme A

Treatment of methyl phenyl sulfoxide with lithium diisopropylamide (LDA)in THF at about −75° C. followed by reaction with 1-Boc-4-piperidone A1at about 21° C. affords sulfoxide A2. Reaction of A2 with potassiumtert-butoxide in refluxing tert-butanol generates allyl alcohol A3 via a[2,3]-sigmatropic rearrangement (WO94/29309). Compound A3 issubsequently reacted with thionyl chloride at about 60° C. for about 25min to provide allyl chloride A4.

Reaction of compound A4 with 3-bromo-4-hydroxybenzonitrile in thepresence of potassium carbonate in acetone furnishes ether A5.Radical-induced cyclization of A5 with tributyltin hydride in thepresence of AIBN and PhMe at about 80° C. affordsspiro[benzofuran-3(2H), 4′-piperidine A6 (Chen, M.-H.; Abraham, J. A.Tetrahedron Lett. 1996, 30, 5233-5234).

Hydrogenation of the nitrile group of A6 in the presence of Raney Nickel(AT about 60 psig H₂) and aqueous 3N sodium hydroxide in EtOH affordsbenzylamine A7.

Reaction of A7 with a reagent such as phthalic anhydride (Pht) intoluene (PhMe) or N,N-diisopropylethylamine (DIPEA),9-fluorenyl-methylcarbonyl chloride (Fmoc-Cl) in DIPEA,2-(trimethylsilyl)ethyl-4-nitrophenyl carbonate (Teoc) in DIPEA followedby removal of the Boc protecting group via HCl or TFA gives A8 as thecorresponding salt (where PG represents a protecting group such as Pht,Fmoc or Teoc).

Coupling of A8 in the presence of a base with either carboxylic acidsand a coupling agent (such as BOP-Cl) in a mixture with DIPEA and CH₂Cl₂or with acid chlorides and sulfonyl chlorides in a mixture with TEA andTHF at about 0° C. then deprotection with methylhydrazine in EtOH atabout 40° C. or with piperidine/DMF or with TFA/CH₂Cl₂ affords thesubstituted 5′-aminomethyl-spiro[benzofuran-3(2H), 4′-piperidine] A9 ofFormula (I).

Scheme B describes the solid-phase synthesis of certain5′-aminomethyl-spiro[benzofuran-3(2H), 4′-piperidine] derivatives A9 ofFormula (I) as a TFA salt.

Scheme B

Removal of the Boc protecting group from A6 with TFA:CH₂Cl₂ followed byreaction of the resulting piperidine with Teoc provides Teoc-protectedintermediate B1 (WO/200190101). Hydrogenation of the nitrile moiety inthe presence of hydrochloric acid in ethanol affords benzylamine B2 asthe hydrochloride salt.

Reaction of B2 with p-nitrophenyl carbonate Wang resin in the presenceof DIPEA and 4-dimethylaminopyridine (DMAP) in DMF followed bydeprotection with tetrabutylammonium fluoride in THF provides theresin-bound intermediate B3. Coupling of B3 with a carboxylic acid(wherein the —C(O)R portion is incorporated into R₃ as a product of thereaction) with N,N′-dicyclohexylcarbodiimide (DIC) and1-hydroxybenzotriazole hydrate (HOBt) followed by cleavage from theresin with trifluoroacetic acid (TFA) furnishes the5-aminomethyl-spiro[benzofuran-3(2H), 4′-piperidine] A1 as the TFA saltof Formula (I), wherein R₃ is carbonyl.

Scheme C describes the synthesis of certain5′-aminomethyl-spiro[benzo[b]thiophene-3(2H), 4′-piperidine] derivativesC6 of Formula (I).

Scheme C

Alkylation of 2-bromotihiophenol with A4 in the presence of potassiumcarbonate in acetone at about 65° C. provides thioether C1.Radical-induced cyclization of C1 with tributyltin hydride in thepresence of AIBN in toluene at about 80° C. affordsspiro[benzo[b]thiophene-3(2H), 4′-piperidine C2 (Chen, M.-H.; Abraham,J. A. Tetrahedron Lett. 1996, 30, 5233-5234).

Removal of the Boc-protecting group from C2 with TFA:CH₂Cl₂ (1:4)followed by partitioning between 0.1 N aqueous sodium hydroxide anddiethyl ether affords the freebase C3. Coupling of C3 with either acarboxylic acid and a coupling agent (such as BOP-Cl) in a mixture withDIPEA and CH₂Cl₂ or with a carboxylic acid chloride or a sulfonylchloride in a mixture with TEA and CH₂Cl₂ at about 0° C. furnishes thecorresponding amide C4.

Tscherniac-Einhorn amidomethylation reaction of C4 withN-(hydroxymethyl)phthalimide in either neat trifilic acid at roomtemperature or a mixture of sulfuric and glacial acetic acids at about60° C. provides C6. Removal of the phthalyl protecting group withmethylhydrazine in ethanol at about 40° C. yields5′-aminomethyl-spiro[benzo[b]-thiophene-3(2H), 4′-piperidine]derivatives C6 of Formula (I).

Scheme D describes the synthesis of certain5′-aminomethyl-spiro[indoline-3,4′-piperidines] derivatives D8 ofFormula (I).

Scheme D

Spiropiperidine D1 can be prepared according to the published method(Ong H H, Profitt J A, Fortunato J, Glamkowski E J, Ellis D B, Geyer HM, Wilker J C, and Burghard H J, Med. Chem., 1983, 26 (7), 981-986).Reacting D1 with formic acid in refluxing toluene provides formamide D2.A Tscherniac-Einhorn amidomethylation reaction of D2 withN-(hydroxymethyl)phthalimide in neat sulfuric acid at room furnishes D3.

Demethylation of D3 with α-chloroethyl chloroformate in the presence of1,8-bis(dimethylamino)naphthalene in refluxing dichloroethane affordscarbamate D4, which converts to piperidine D5 with hydrochloric acid inrefluxing methanol (Olofson, R. A.; Martz, J. T.; Senet, J. P.; Piteau,M.; Malfroot, T. J. Org. Chem. 1984, 49 (11), 2081-2082).

Selective coupling of the piperidine nitrogen of D5 withN-hydroxysuccinimide ester D6 in THF yields the corresponding amide D7(Xie J-S, Huang C Q, Fang Y-Y and Zhu Y-F, Tetrahedron 2004, 60 (22),4875-4878). Subsequent coupling of the D7 indoline nitrogen with eithera carboxylic acid chloride or a sulfonyl chloride according to theconditions of Schemes A-C affords the corresponding carboxamides andsulfonamides of the 5′-aminomethyl-spiro[indoline-3,4′-piperidine]derivatives D8 of Formula (I).

Scheme E describes the synthesis of certain2,3-dihydro-spiro[1H-indene-1,4′-piperidine] derivatives E7 of Formula(I).

Scheme E

Reduction of 5-bromo-1-indanone E1 with sodium borohydride in MeOHfollowed by dehydration of the resulting alcohol with sulfuric acid inrefluxing benzene at about 80° C. affords 6-bromo-1H-indene E2(CAS#33065-61-1; see, Young J R, Huang S X, Walsh T F, Wyvratt M J, YangY T, Yudkovitz J B, Cui J, Mount G R, Ren R N, Wu T-J, Shen X, Lyons KA, Mao A-H, Carlin J R, Karanam B V, Vincent S H, Cheng K and Goulet MT, Bioorg. Med. Chem. Lett. 2002, 12 (5), 827-832).

Treatment of E2 with lithium bis(trimethylsilyl)amide at 0° C. in THFfollowed by alkylation with N-Boc-N,N-bis(2-chloroethyl)amine providesspiro[1H-indene-1,4′-piperidine] E3 (CAS#158628-80-9; see, Efange S M N,Khare A B, Foulon C, Akella S K and Parsons S M, J. Med. Chem. 1994, 37(16), 2574-82).

Formylation of E3 with sodium formate and carbon monoxide in thepresence of tris(3-chlorophenyl)phosphine andbis(triphenylphosphine)-palladium(II) bromide in DMF at about 110° C.furnishes aldehyde E4 (Okano T, Harada N and Jitsuo Kiji J, Bull. Chem.Soc. Jpn 1994, 67 (8), 2329-2332). Reaction of E4 with hydrazine in EtOHfollowed by hydrogenation of the hydrazone and alkene moieties of E5 viaPtO₂ in EtOH under hydrogen provides benzylamine E5.

Reaction of E5 with phthalic anhydride in the presence of DIPEA inrefluxing toluene followed by removal of the Boc-group with TFA inCH₂Cl₂ provides piperidine E6. Under foregoing conditions, coupling ofE6 with either a carboxylic acid in a mixture with EDC and DMF, acarboxylic acid chloride or a sulfonyl chloride in TEA and in CH₂Cl₂ atabout 0° C. followed by deprotection with methylhydrazine in ethanol atreflux affords the corresponding carboxamide and sulfonamide derivativesof 2,3-dihydro-spiro[1H-indene-1,4′-piperidine] E7 of Formula (I).

Scheme F describes the synthesis of certainspiro[3H-indole-3,4′-piperidin]-2(1H)-ones F7 of Formula (I).

Scheme F

Reacting 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid F1 withthionyl chloride in the presence of pyridine in CH₂Cl₂ provides thecorresponding acid chloride, which is subsequently reacted with4-amino-3-bromobenzonitrile in a mixture with DMAP and CH₂Cl₂ to furnishanilide F2. Reaction of F2 with p-methoxybenzyl chloride in the presenceof potassium fluoride on alumina in refluxing acetonitrile provides F3.

Palladium catalyzed intramolecular amide α-arylation of F3 withtris(dibenzylideneacetone)dipalladium(0) and sodium tert-butoxide in thepresence of (+/−)-2,2′-bis(diphenylphosphino)-1,4-binaphthalene (BINAP)in 1,4-dioxane at about 95-110° C. generates compound F4 (see, Freund Rand Mederski W K R, Helv. Chim. Acta 2000, 83 (6), 1247-1255). Oxidativeremoval of the p-methoxybenzyl protecting group with ammonium cerium(IV)nitrate in a mixture of water and acetonitrile provides F5.

Removal of the Boc-protecting group of F5 with TFA in CH₂Cl₂ followed bycoupling of the resulting piperidine with a carboxylic acid, carboxylicacid chloride, or a sulfonyl chloride according to the conditions ofScheme E affords the corresponding carboxamide and sulfonamidederivatives F6. Catalytic hydrogenation of F6 with Raney nickel underhydrogen in a mixture of 3N aqueous sodium hydroxide and ethanolfurnishes the corresponding carboxamide and sulfonamide derivatives ofspiro[3H-indole-3,4′-piperidin]-2(1H)-ones F7 of Formula (I).

Scheme G describes the synthesis of certainspiro[1H-isoindole-1,4′-piperidin]-3(2H)-ones G7 of Formula (I).

Scheme G

Reaction of methyl 2-bromo-4-(bromomethyl)benzoate G1 (CAS#128577-48-0)with potassium phthalimide in DMF followed by demethylation with lithiumiodide in refluxing pyridine provides carboxylic acid G2. Reaction of G2with refluxing thionyl chloride provides the acid chloride G3.

Condensation of 2,4-dimethoxybenzylamine G4 with 1-Boc-4-piperidone(CAS#79099-07-3) in refluxing toluene furnishes imine G5. Reaction of G5with G3 in toluene at about 80° C. provides amide G6.

Intramolecular Heck cyclization of G6 with palladium(II) acetate in thepresence of tricyclopentylphosphine, and dicyclopentylmethylamine inN,N-dimethylacetamide (DMA) at about 100° C. provides isoindolone G7.Removal of the Boc-protecting group with TFA in CH₂Cl₂ followed bycatalytic hydrogenation via 10% Pd/C under hydrogen in EtOH affordsspiropiperidine G8.

Coupling of G8 with a carboxylic acid, carboxylic acid chloride, or asulfonyl chloride according to the conditions of Scheme C affords thecorresponding carboxamide and sulfonamide derivatives. Removal of thephthalyl protecting group with methylhydrazine at about 40° C. followedby removal of the dimethoxybenzyl protecting group with neat TFAprovides the corresponding carboxamide and sulfonamide derivatives G9 ofFormula (I).

Scheme H describes the solution-phase synthesis of certain5-aminomethyl-spiro[benzofuran-3(2H), 4′-piperidine] derivatives H3, H4,H5, and H6 of Formula (I).

Scheme H

Removal of the Boc group from A6 (Scheme A) with trifluoroacetic acidfollowed by coupling with either carboxylic acids and a coupling agent(such as BOP-Cl) in a mixture with DIPEA and CH₂Cl₂ or with acidchlorides and sulfonyl chlorides in a mixture with TEA and THF at about0° C. generates nitrile H1.

Pinner reaction of H1 with hydrochloric acid in ethanol at 5° C.,followed by neutralization with 3 N NaOH affords ethyl imidate H2 as thefree base.

Compound H2 is reacted with anhydrous ammonia, mono- or dialkylamine,hydroxylamine or hydrazine with subsequent purification by reverse-phaseHPLC to yield H3, H4, H5 and H6, respectively.

Specific Examples General Information and Procedures

Commercially available reagents were used without purification unlessspecifically necessary. All reactions were conducted under argon ornitrogen in rigorously dried solvents with magnetic stirring at roomtemperature unless noted otherwise. Multiple extractions are designatedwithin parentheses; e.g., “(3×)” indicates 3 extractions. Solutions andresidues were not heated above 40° C. while concentrating in vacuo.Normal-phase preparative chromatography was performed either on an IscoCombiflash Separation System Sg 100c equipped with a Biotage FLASH Si40M silica gel cartridge (KP-Sil® Silica, 32-63 μm, 60 Å; 40×270 mm)eluting at 35 mL/min or on a Waters Delta Prep 3000 equipped with 2PrepPak® silica gel cartridges (Porasil® Silica, 55-105 μm, 57×300 mm)connected in series eluting at 120 mL/min; both systems had peakdetection at 254 nm and solvent gradient times of 60 min.

Reverse-phase preparative chromatography was performed on a GilsonPreparative HPLC system equipped with a Kromasil C-18 column (2.5×50 cm;10 μm, 100 Å) eluting at 50 mL/min with detection at 220 nm; solventgradients were conducted over a 30 min period and fractions werecollected over 40 min. Reverse-phase chromatography fractions werelyophilized on a FTS Systems Flexi-Dry MP lyophilizer. Melting pointswere determined on a Thomas-Hoover apparatus calibrated with a set ofmelting point standards. ¹H NMR spectra were acquired at 300.14 MHz on aBruker Avance-300 spectrometer in CD₃OD unless indicated otherwise,using Me₄Si as an internal standard. NMR abbreviations used: AB_(q), ABquartet; br, broad; d, doublet; dd, doublet of doublets; dt, doublet oftriplets; m, multiplet; ov, overlapping; q quartet; s, singlet; t,triplet. Electrospray (ES) mass spectra were obtained on a MicromassPlatform LC single quadrupole mass spectrometer in the positive mode.Chemical-ionization mass spectra (CI-MS) were recorded on a Finnigan3300 mass spectrometer with methane as the reagent gas.

The following examples are offered by way of illustration; the inventionshould not be construed as being limited by the chemical reactions andconditions expressed.

Example 11-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-benzo[b]furan](Cpd 3)

Step A. 4-benzenesulfinylmethyl-4-hydroxy-piperidine-1-carboxylic acidtert-butyl ester (CAS#221142-27-4)

A solution of n-butyllithium (96 mL of 2.5 M in hexanes, 0.240 mol) wasadded dropwise at −75° C. to a solution of diisopropylamine (33.2 mL,0.237 mol) in THF (150 mL) with mechanical stirring under argon andstirred for 30 min. To this solution was added a solution of (±)-methylphenyl sulfoxide (33.2 g, 0.237 mol) in THF (40 mL) dropwise over 15 minat −75° C. The reaction mixture was quickly warmed to 5° C., stirred for20 min, cooled back down to −75° C., treated with a solution of1-Boc-4-piperidone (46.9 g, 0.235 mol; CAS#79099-07-3) in THF (200 mL)and slowly warmed to room temperature over 18 h. The resulting lightyellow suspension was quenched by the addition of solid ammoniumchloride (39 g, 0.729 mol) and concentrated in vacuo. The residue waspartitioned between EtOAc and water. The aqueous layer was extractedwith EtOAc (2×) and the combined EtOAc extracts were washed with brine(2×), dried (MgSO₄), filtered and concentrated in vacuo to afford 1a(64.3 g, 80%) as an off-white solid: ¹H NMR (CDCl₃) δ 7.70-7.50 (m, 5H),4.20 (br s, 1H), 4.05-3.80 (m, 2H), 3.40-3.15 (m, 2H), 3.06, 2.70(AB_(q), J_(ab)=13.4 Hz, 2H), 2.19-2.13 (m, 1H), 1.88-1.50 (m, 3H), 1.46(s, 9H); MS (ES) m/z 340.2 (MH)⁺.

Step B. 3-hydroxy-4-methylene-piperidine-1-carboxylic acid tert-butylester (CAS#159635-22-0)

Potassium tert-butoxide (21.7 g, 0.193 mol) was combined with 1a (50.5g, 0.149 mol) in tert-butanol and the resulting yellow suspension washeated at reflux with mechanical stirring under argon for 2 h. Thereaction mixture was cooled to room temperature, quenched by theaddition of solid ammonium chloride (24.0 g, 0.446 mol), stirred for 10min, and concentrated in vacuo. The residue was partitioned betweenwater and EtOAc and the aqueous layer was extracted with EtOAc (2×). Thecombined EtOAc extracts were washed with brine (2×), dried (MgSO₄),filtered through filter agent, and concentrated in vacuo. The brownresidue was purified by chromatography on silica gel on an IscoCombiflash chromatograph eluting with hexane/EtOAc (4:1) to furnish 1bas an amber solid (23.3 g, 74%): ¹H NMR (CDCl₃) δ 5.03 (s, 1H), 4.88 (s,1H), 4.20-4.05 (m, 1H), 3.75 (dd, J=12.9 Hz, 3.9 Hz, 1H), 3.65-3.40 (m,1H), 3.35-3.10 (m, 2H), 2.50-2.46 (m, 1H), 2.20-2.05 (m, 2H), 1.95 (brs, 1H), 1.47 (s, 9H); MS (ES) m/z 236.2 (M+Na)⁺.

Step C. 4-chloromethyl-3,6-dihydro-(2H)-pyridine-1-carboxylic acidtert-butyl ester (CAS#159635-22-0)

A solution of 1b (6.07 g, 0.0285 mol) in toluene (150 mL) was heated to60° C. and treated in one portion with thionyl chloride (2.50 mL, 0.0342mol). After 25 min at 60° C., the reaction mixture was quickly cooled to5° C. and poured into saturated aqueous NaHCO₃ that was previouslycooled to 5° C. The layers were separated and the organic layer wasextracted with saturated aqueous NaHCO₃ (2×), brine (2×), dried (MgSO₄),filtered through filer agent, and concentrated in vacuo to give 1c as abrown oil (3.84 g, 58%): ¹H NMR (CDCl₃) δ 5.95-5.70 (m, 1H), 4.03 (s,2H), 4.00-3.90 (m, 2H), 3.53 (t, J=5.7 Hz, 2H), 2.30-2.15 (m, 2H), 1.47(s, 9H); MS (CI) m/z 232.2 (MH)⁺.

Step D.4-(2-bromo-4-cyano-phenoxymethyl)-3,6-dihydro-(2H)-pyridine-1-carboxylicacid tert-butyl ester

Finely ground K₂CO₃ (12.5 g, 0.0906 mol) was added to a solution of3-bromo-4-hydroxylbenzonitrile (6.58 g, 0.0332 mol) and 1c (7.00 g,0.0302 mol) in acetone (164 mL). The reaction mixture was heated atreflux for 60 h while stirring under argon. The reaction mixture wasfiltered and the filtrate was concentrated in vacuo and partitionedbetween EtOAc and 5% aqueous K₂CO₃. The organic layer was extracted 5%aqueous K₂CO₃ (2×), brine (2×), dried (MgSO₄), filtered through filteragent and concentrated in vacuo to furnish 1d (10.9 g, 92%) as a tansolid: ¹H NMR (CDCl₃) δ 7.84 (d, 1H, J=2.0 Hz), 7.58 (dd, 1H, J=8.6 Hz,2.0 Hz), 6.92 (d, 1H, 8.6 Hz), 5.80-5.70 (m, 1H), 4.55 (s, 2H),4.00-3.90 (m, 2H), 3.57 (t, 2H, J=5.7 Hz), 2.30-2.15 (m, 2H), 1.48 (s,9H); MS (ES) m/z 415.0 (M+Na)⁺.

Step E.1-(tert-butyloxy)carbonyl-5′-cyano-spiro[piperidine-4,3′-benzo[b]furan]

A solution of 1d (10.7 g, 0.0271 mol) and Bu₃SnH (10.9 mL, 0.0407 mol)in toluene (1360 mL) was treated with AIBN (0.232 g, 0.0014 mol). Thereaction mixture was heated at 80° C. under argon for 4 h, cooled toroom temperature, and concentrated in vacuo. The residue was dissolvedin 250 mL of EtOAc, cooled to 5° C. and treated with DBU (11 mL, 0.075mol). Bromine (ca. 6 mL) was added dropwise until a brown endpoint wasreached. The resulting precipitate was removed by filtration through abed of silica gel. The filtrate was extracted with 1 N aqueous Na₂S₂O₄(2×), brine (2×), dried (MgSO₄), filtered through filter agent andconcentrated in vacuo to give a yellow solid. This solid was purified bychromatography on silica gel eluting with 10-30% EtOAc in hexane to give1e (5.87 g, 69%) as a white solid: ¹H NMR (CDCl₃) δ 7.48 (dd, 1H, J=8.3Hz, 1.7 Hz), 7.37 (d, J=1.7 Hz), 6.86 (d, 1H, J=8.3 Hz), 4.50 (s, (2H)),4.20-4.02 (m, 2H), 2.95-2.75 (m, 2H), 1.95-1.65 (ov m, 4H), 1.49 (s,9H); MS (ES) m/z 314.9 (MH)⁺, 336.9 (M+Na)⁺.

Step F.1-(tert-butyloxy)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-benzo[b]furan]

A solution of 1e (4.00 g, 0.0127 mol) in mixture of ethanol (160 mL) and3N aqueous NaOH (60 mL) was treated with a 50% aqueous suspension ofRaney nickel (1.46 g) and placed on a Parr hydrogenator under 60 psig ofhydrogen for 16 h. The reaction mixture was filtered through filteragent and the filtrate was concentrated in vacuo. The residue waspartitioned between water and CHCl₃. The aqueous layer was extractedagain with CHCl₃ (2×) and the combined CHCl₃ extracts were washed withbrine (2×), dried (K₂CO₃), filtered through filter agent, andconcentrated in vacuo to afford 1f (4.06 g, 100%) as a clear viscousoil: ¹H NMR (CDCl₃) δ 7.10-7.00 (ov m, 2H), 6.76 (d, 1H, J=8.7 Hz), 4.41(s, 2H), 4.40-4.00 (m, 2H), 3.80 (s, 2H), 3.05-2.80 (m, 2H), 2.00-1.60(ov m, 4H), 1.49 (s, 9H), 1.33 (br s, 2H); MS (ES) m/z 318.9 (MH)⁺.

Step G.1-(tert-butyloxy)carbonyl-5′-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-spiro[piperidine-4,3′-(2H)-benzo[b]furan]

A solution of phthalic anhydride (1.74 g, 0.0118 mol), 1f (3.74 g,0.0118 mol), and N,N-diisopropylethylamine (2.87 mL, 0.0165 mol) intoluene (118 mL) was heated at reflux under argon with azeotropicremoval of water for 14 h. The reaction mixture was cooled to roomtemperature, extracted with 10% aqueous citric acid (3×) and brine (2×),dried (MgSO₄), filtered through filter agent and concentrated in vacuo.The residue was purified by chromatography on silica gel on a IscoCombiflash chromatograph eluting with hexane/EtOAc (4:1) to furnish 1gas a white foam (3.56 g, 68%): ¹H NMR (CDCl₃) δ 7.84 (dd, 2H, J=5.4 Hz,3.1 Hz), 7.70 (dd, 2H, J=5.4 Hz, 3.1 Hz), 7.35-7.20 (ov m, 2H), 6.73 (d,1H, J=8.2 Hz), 4.77 (s, 2H), 4.38 (s, 2H), 4.20-4.00 (m, 2H), 2.95-2.80(m, 2H), 1.95-1.60 (m, 4H), 1.50 (s, 9H); MS (ES) m/z 471.2 (M+Na)⁺.

Step H.5′-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-spiro[piperidine-4,3′-benzo[b]furan]Hydrochloride (1:1)

A solution of 1g (3.54 g, 0.0079 mol) in dichloromethane (60 mL) wastreated with trifluoromethylacetic acid (20 mL), stirred under anitrogen atmosphere for 1 h and concentrated in vacuo. The residue wasdissolved in methanol (150 mL) and treated with 4N HCl in 1,4-dioxane (6mL). The resulting white suspension was concentrated in vacuo, partiallydissolved in methanol (150 mL), treated with 4N HCl in 1,4-dioxane (6mL) and concentrated in vacuo. The foregoing process was repeated yetagain and the resulting white solid was suspended in diethyl ether (200mL) and stirred at room temperature over 16 h. The resulting whiteprecipitate was isolated by filtration, washed with diethylether, anddried in vacuo to give 1 h (2.99 g, 98%) as a white solid: ¹H NMR(CD₃OD) δ 7.95-7.80 (ov m, 4H), 7.35-7.10 (ov m, 2H), 6.76 (d, 1H, J=8.2Hz), 4.79 (s, 2H), 4.50 (s, 2H), 3.55-3.40 (m 2H), 3.14 (dt, 2H, J=13.0Hz, 3.4 Hz), 2.20-2.05 (m, 2H), 2.05-1.90 (m, 2H); MS (ES) m/z 348.9(MH)⁺.

Step I.1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-spiro[piperidine-4,3′-(2H)-benzo[b]furan]

Bis(2-oxo-3-oxazolidinyl)phosphinic chloride (2.37 g, 0.0093 mol) wasadded to a slurry of 1i (2.99 g, 0.0078 mol),5-(2-phenyleth-1-ynyl-2-furoic acid, 1.81 g, 0.0085 mol), andN,N-diisopropylethylamine (6.00 mL, 0.0344 mol) in dichloromethane (156mL) while stirring under argon. After 75 min, the resulting ambersolution was concentrated in vacuo and partitioned between EtOAc and 10%aqueous citric acid. The organic layer was extracted with 10% aqueouscitric acid (2×), saturated aqueous NaHCO₃ (3×), brine (3×), dried(MgSO₄) and concentrated in vacuo to furnish 1i (4.18 g, 99%) as a tansolid: ¹H NMR (CDCl₃) δ 7.90-7.77 (m, 2H), 7.77-7.62 (m, 2H), 7.60-7.50(m, 2H), 7.50-7.30 (ov m, 3H), 7.30-7.20 (m, 2H), 7.13 (d, 1H, J=3.5Hz), 6.80-6.65 (ov m, 2H), 4.77 (s, 2H), 4.62-4.50 (m, 2H), 4.46 (s,2H), 3.30-2.90 (br m, 2H), 2.08-1.90; (m, 2H); 1.90-1.75 (m, 2H); MS(ES) m/z 542.7 (MH)⁺.

Step J.1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan]Benzoate (1:1) (Cpd 3)

A slurry of 1i (4.25 g, 0.0078 mol) in ethanol (78 mL) was treated withmethylhydrazine (7.8 mL, 0.1466 mol) was stirred at room temperatureunder argon for 16 h. Additional portions of ethanol (78 mL) andmethylhydrazine (7.8 mL, 0.1466 mol) were added and the reaction mixturewas heated at 40° C. for 5.5 h. The resultant yellow solution was cooledto room temperature and concentrated in vacuo. The residue was purifiedby reversed phase chromatography eluting with 25-90% MeCN/H₂O/0.2% TFAto give the TFA salt of the title compound as an off-white solid. Thismaterial was partitioned between 1 N aqueous NaOH and chloroform and thebasic aqueous layer was extracted with chloroform (2×) and the combinedorganic extracts were washed with brine (2×), dried (Na₂SO₄), filteredthrough filter agent and concentrated in vacuo to provide the freebaseof Compound 1 as a tan foam (2.12 g, 66%). The freebase (2.49 g, 0.0060mol) was combined with benzoic acid (0.737 g, 0.0060 mol) was dissolvedin boiling ethanol (40 mL) and allowed to crystallize first at roomtemperature and then at 5° C. The resulting crystals were isolated byfiltration, washed with diethylether, and dried in vacuo over 16 h at80° C. to afford Compound 3 (2.15 g, 66%) as the benzoate salt: mp179-181° C.; ¹H NMR (CD₃OD) δ 7.88-7.76 (m, 2H), 7.50-7.38 (m, 2H),7.38-7.15 (ov m, 7H), 7.13 (dd, 1H, J=8.2 Hz, 1.9 Hz) 6.99 (d, 1H, J=3.6Hz), 6.76 (d, 1H, J=3.6 Hz), 6.71 (d, 1H, J=8.2 Hz), 4.47 (s, 2H),4.47-4.30 (m, 2H), 3.92 (s, 2H), 3.50-2.90 (br m, 2H), 1.97-1.80 (m,2H), 1.80-1.65 (m, 2H); MS (ES) m/z 413.3 (MH)⁺.

Using the procedure of Example 1 and suitable reagents, startingmaterials and reaction conditions, other compounds representative of thepresent invention may be prepared by those skilled in the art, such as:

Cpd Name and Data 41-(3-benzoyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.90-7.80 (m, 4H), 7.75-7.64 (m, 3H),7.57-7.53 (m, 2H), 7.31 (d, J = 1.8 Hz, 1H), 7.23 (dd, J = 2.0 Hz, J =8.2 Hz, 1H), 6.82 (dd, J = 3.4 Hz, J = 8.2 Hz, 1H), 4.67-4.57 (m, 3H),4.04 (s, 2H), 3.86-3.78 (m, 1H), 3.35-3.25 (br m, 1H), 3.20-3.12 (m,1H), 2.03-1.77 (m, 4H). C₂₇H₂₆N₂O₃; MS (ESI) m/z 427 (MH)⁺. 61-(4-benzoyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.88 (d, J = 8.2 Hz, 2H), 7.80 (d, J =7.1 Hz, 2H), 7.70 (m, 5H), 7.34 (d, J = 1.9 Hz, 1H), 7.24 (dd, J = 1.9Hz, J = 8.2 Hz, 1H), 6.83 (d, J = 8.2 Hz, 1H), 4.58 (br s, 3H), 4.05 (s,2H), 5.85-3.75 (m, 1H), 3.28-3.18 (m, 2H), 2.03-1.78 (m, 4H).C₂₇H₂₆N₂O₃; MS (ESI) m/z 427 (MH)⁺. 71-(9-oxo-10,10-dioxo-thioxanthen-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 8.44 (d, J =8.0 Hz, 1H), 8.36 (dd, J = 1.1 Hz, J = 7.7 Hz, 1H), 8.24 (d, J = 1.4 Hz,1H), 8.19 (d, J = 7.7 Hz, 1H), 8.04-7.89 (m, 3H), 7.36 (d, J = 1.8 Hz,1H), 7.24 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 6.83 (d, J = 8.2 Hz, 1H),4.57 (m, 3H), 4.06 (s, 2H), 3.70-3.50 (br m, 1H), 3.32-3.20 (m, 2H),2.03-1.78 (m, 4H). C₂₇H₂₄N₂O₅S; MS (ESI) m/z 489 (MH)⁺. 81-(9-oxo-fluoren-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.77-7.37 (m, 7H), 7.27-7.25 (m, 1H),7.14 (s, 1H), 6.84 (d, J = 8.2 Hz, 1H), 4.82 (m, 1H), 4.64-4.51 (m, 2H),4.05 (d, J = 15.2 Hz, 2H), 3.68 (d, J = 13.9 Hz, 1H), 3.38-3.27 (m, 2H),2.12-2.00 (m, 2.5H), 1.69 (m, 1.5H). C₂₇H₂₄N₂O₃; MS (ESI) m/z 425 (MH)⁺.9 1-(4-benzoimidazol-1-ylmethylcarbonylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ9.14 (s, 1H), 7.85-7.73 (m, 4H), 7.62-7.59 (m, 2H), 7.49 (d, J = 8.6 Hz,2H), 7.33 (s, 1H), 7.23 (d, J = 8.3 Hz, 1H), 6.84 (d, J = 8.3 Hz, 1H),5.45 (m, 3H), 4.58 (m, 4H), 4.06 (s, 2H), 3.15 (m, 1H), 2.00-1.80 (m,4H). C29H29N5O3; MS (ESI) m/z 496 (MH)⁺. 101-(4-benzoimidazol-1-ylmethyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 9.5 (s, 1H),7.87 (d, J = 7.3 Hz, 1H), 7.81 (d, J = 7.2 Hz, 1H), 7.66-7.50 (m, 6H),7.31 (d, J = 1.7 Hz, 1H), 7.26 (dd, J = 1.8 Hz, J = 8.2 Hz, 1H), 6.81(d, J = 8.2 Hz, 1H), 5.81 (s, 2H), 4.60-4.40 (br m, 3H), 4.04 (s, 2H),3.75-3.60 (br m, 1H), 3.20-3.05 (br m, 2H), 2.03-1.72 (m, 4H).C₂₈H₂₈N₄O₂; MS (ESI) m/z 453 (MH)⁺. 111-(4-aminosulfonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 8.02 (d, J = 8.4 Hz, 2H), 7.64 (d,J = 8.5 Hz, 2H), 7.35 (s, 1H), 7.26 (d, J = 8.3 Hz, 1H), 6.85 (d, J =8.2 Hz, 1H), 4.56 (br s, 3H), 4.07 (s, 2H), 3.75-3.65 (br m, 1H),3.33-3.31 (br m, 2H), 1.93-1.77 (m, 4H). C₂₀H₂₃N₃O₄S; MS (ESI) m/z 402(MH)⁺. 121-[5-(4-chloro-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.78 (d, J = 8.6 Hz, 2H), 7.47(d, J = 8.6 Hz, 2H), 7.33 (d, J = 1.8 Hz, 1H), 7.26 (dd, J = 1.9 Hz, J =8.2 Hz, 1H), 7.18 (d, J = 3.7, 1H), 7.00 (d, J = 3.7, 1H), 6.86 (d, J =8.2 Hz, 1H), 4.64-4.57 (m, 4H), 4.06 (s, 2H), 3.68-3.20 (br m, 2H),2.09-1.90 (m, 4H). C₂₄H₂₃ClN₂O₃; MS (ESI) m/z 423 (MH)⁺. 131-(5-chloro-benzo[b]-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.75 (s, 1H), 7.57 (d, J = 8.8Hz, 1H), 7.45 (d, J = 2.1 Hz, 1H), 7.36 (s, 1H), 7.31 (s, 1H), 7.22 (m,1H), 6.84 (d, J = 8.2 Hz, 1H), 4.61 (br s, 3H), 4.04 (s, 2H), 3.60-3.00(br m, 3H), 2.03-1.84 (br m, 4H). C₂₂H₂₁ClN₂O₃; MS (ESI) m/z 397 (MH)⁺.14 1-(1-phenyl-2-methyl-benzoimidazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.90 (s, 1H),7.73 (m, 3H), 7.60 (m, 2H), 7.55 (m, 1H), 7.40 (d, J = 8.5 Hz, 1H), 7.34(d, J = 1.7 Hz, 1H), 7.23 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H) 6.82 (d, J =8.2 Hz, 1H), 4.56 (br s, 3H), 4.04 (s, 2H), 3.85-3.70 (br m, 1H),3.40-3.20 (m, 2H), 2.69 (s, 3H), 2.05-1.70 (m, 4H). C₂₈H₂₈N₄O₂; MS (ESI)m/z 453 (MH)⁺. 151-[4-(3-trifluoromethyl-phenyl)-phenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.94 (m, 2H),7.80 (d, J = 8.3 Hz, 2H), 7.70 (m, 2H), 7.60 (d, J = 8.3 Hz, 2H), 7.34(d, J = 1.8 Hz, 1H), 7.24 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H) 6.83 (d, J =8.2 Hz, 1H), 4.58 (br s, 3H), 4.05 (s, 2H), 3.90-3.85 (br m, 1H),3.32-3.00 (m, 2H) 1.91-1.78 (m, 4H). C₂₇H₂₅F₃N₂O₂; MS (ESI) m/z 467(MH)⁺. 161-benzothiazol-6-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 9.34 (s, 1H), 8.23 (s, 1H), 8.17 (d, J =8.5 Hz, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.34 (s, 1H), 7.24 (d, J = 8.2Hz, 1H) 6.83 (d, J = 8.2 Hz, 1H), 4.57 (br s, 3H), 4.05 (s, 2H),3.90-3.75 (br m, 1H), 3.32-3.00 (m, 2H) 2.10-1.78 (m, 4H). C₂₁H₂₁N₃O₂S;MS (ESI) m/z 380 (MH)⁺. 171-{4-[(4-benzoxazol-2-yl)-pyrazol-1-yl]-phenyl}carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 9.12 (s, 1H),8.41 (s, 1H), 8.05 (d, J = 8.7 Hz, 2H), 7.71-7.64 (m, 4H), 7.44-7.34 (m,3H), 7.24 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H) 6.83 (d, J = 8.2 Hz, 1H),4.58 (br s, 3H), 4.06 (s, 2H), 3.90-3.75 (br m, 1H), 3.32-3.00 (m, 2H)2.05-1.85 (br m, 4H). C₃₀H₂₇N₅O₃; MS (ESI) m/z 506 (MH)⁺. 181-(3-phenylsulfonylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.76 (m, 2H), 7.57-7.12 (m,9H), 6.82 (d, J = 8.2 Hz, 1H), 4.54 (br s, 3H), 4.06 (s, 2H), 3.60-3.45(br m, 1H), 3.29-3.08 (m, 2H) 2.04-1.70 (br m, 4H). C₂₆H₂₇N₃O₄S; MS(ESI) m/z 478 (MH)⁺. 191-(3-thien-2-ylmethylcarbonylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.94 (d, J =1.7 Hz, 1H), 7.51-7.17 (m, 6H), 7.01-6.95 (m, 2H), 6.81 (d, J = 8.2 Hz,1H), 4.54 (br s, 3H), 4.04 (s, 2H), 3.91 (s, 2H), 3.80-3.70 (br m, 1H),3.10 (m, 2H) 2.03-1.74 (br m, 4H). C₂₆H₂₇N₃O₃S; MS (ESI) m/z 462 (MH)⁺.201-(3-benzodioxol-5-yl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.68 (d, J = 8.0 Hz, 1H), 7.61 (s,1H), 7.52 (t, J = 7.6 Hz, 1H), 7.38 (d, J = 7.6 Hz, 1H), 7.33 (d, J =1.7 Hz, 1H), 7.23 (dd, J = 1.6 Hz, J = 6.8 Hz, 1H), 7.12 (m, 2H), 6.91(d, J = 8.7 Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H), 6.00 (s, 2H), 4.56 (br s,3H), 4.04 (s, 2H), 3.85-3.75 (br m, 1H), 3.32-3.14 (m, 2H) 2.03-1.76 (brm, 4H). C₂₇H₂₆N₂O₄; MS (ESI) m/z 443 (MH)⁺. 211-[3-(5-chloro-pyrimidin-2-yl)thiophenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 8.54 (s, 2H),7.23 (m, 2H), 7.58 (m, 2H), 7.30 (d, J = 1.7 Hz, 1H), 7.23 (d, J = 8.2Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H), 4.57 (br s, 3H), 4.03 (s, 2H),3.90-3.75 (br m, 1H), 3.12 (m, 2H), 1.98-1.78 (br m, 4H). C₂₄H₂₃ClN₄O₂S;MS (ESI) m/z 467 (MH)⁺. 221-(5-trifluoromethyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.30 (d, J = 1.6 Hz, 1H), 7.24(dd, J = 1.7 Hz, J = 8.2 Hz, 1H), 7.16 (m, 1H), 7.11 (m, 1H), 6.83 (d, J= 8.2 Hz, 1H), 4.59 (s, 2H), 4.52-4.08 (br m, 2H), 4.04 (s, 2H),3.55-3.45 (br m, 1H), 3.20-3.10 (br m, 1H), 2.05-1.85 (m, 4H).C₁₉H₁₉F₃N₂O₃; MS (ESI) m/z 381 (MH)⁺. 351-[5-(2-fluoro-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.65-7.55 (m,1H), 7.54-7.40 (m, 1H), 7.31 (d, J = 1.8 Hz, 1H), 7.11 (d, J = 3.7 Hz,1H), 6.91 (d, J = 3.7 Hz, 1H), 6.83 (d, J = 1.8 Hz, 1H), 4.60 (s, 2H),4.59-4.40 (m, 2H), 4.03 (s, 2H), 3.70-2.90 (br m, 4H), 2.08-1.80 (m,4H). C₂₆H₂₃FN₂O₃; MS (ESI) m/z 431 (MH)⁺. 109(E)-1-(phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.65-7.59 (m, 3H), 7.44-7.35 (m, 3H),7.28-7.19 (m, 3H), 6.83 (d, J = 8.2 Hz, 1H), 4.58 (br s, 3H), 4.31 (brd, J = 14.1 Hz, 1H), 4.03 (s, 2H), 3.40 (br t, J = 12.0 Hz, 1H), 3.02(br t, J = 12.1 Hz, 1H), 2.03-1.75 (br m, 4H). C₂₂H₂₄N₂O₂; MS (ESI) m/z349 (MH)⁺. 1101-benzothien-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.95-7.87 (m, 2H), 7.66 (s, 1H),7.58-7.41 (m, 2H), 7.33 (d, J = 1.9 Hz, 1H), 7.24 (dd, J = 1.9 Hz, J =8.2 Hz, 1H), 6.83 (d, J = 8.2 Hz, 1H), 4.59 (s, 2H), 4.50-4.40 (br m,2H), 4.05 (s, 2H), 3.35-3.30 (br m, 2H), 2.06-1.49 (m, 4H). C₂₂H₂₂N₂O₂S;MS (ESI) m/z 379 (MH)⁺. 1601-benzo[b]furan-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.72 (d, J = 7.8 Hz, 1H), 7.57 (d, J =8.3 Hz, 1H), 7.45 (t, J = 7.3 Hz, 1H), 7.39-7.30 (m, 2H), 7.24 (dd, J =1.7 Hz, J = 8.2 Hz, 1H), 6.83 (d, J = 8.2 Hz, 1H), 4.59 (s, 2H), 4.52(br s, 2H), 4.05 (s, 2H), 3.55-3.40 (br m, 1H), 3.25-3.15 (br m, 1H),2.09-1.86 (m, 4H). C₂₂H₂₂N₂O₃; MS (ESI) m/z 363 (MH)⁺. 312(E)-1-(2,3-difluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.63 (d, J = 15.6 Hz, 1H),7.47 (d t, J = 1.5 Hz, J = 7.8 Hz, 1H), 7.25 (s, 1H), 7.22-7.09 (m, 4H),6.73 (d, J = 8.2 Hz, 1H), 4.48 (s, 2H), 4.18 (br d, J = 14.2 Hz, 2H),3.93 (s, 2H), 3.31 (br t, J = 11.4 Hz, 1H), 2.94 (br t, J = 11.0 hz,1H), 1.98-1-78 (m, 4H). C₂₂H₂₂F₂N₂O₂; MS (ESI) m/z 385 (MH)⁺.

Example 21-[(5-phenylthio)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-benzo[b]furan](Cpd 23)

Step A.1-[2-(trimethylsilyl)ethoxy]carbonyl-5′-cyano-spiro[piperidine-4,3′-benzo[b]furan]

Compound 1f, (4.79 g, 15.2 mmol; Example 1) was combined withtrifluoroacetic acid (20 mL) in dry dichloromethane (50 mL) and stirredat room temperature for 15 minutes. The reaction mixture wasconcentrated in vacuo and the residue was dissolved in acetonitrile (70ml) and treated with 4-dimethylaminopyridine (1.9 g, 15.2 mmol),triethylamine (6.2 g, 60.8 mmol) and4-nitrophenyl-2-(trimethylsilyl)ethyl carbonate (4.3 g, 15.2 mmol). Theresulting reaction mixture was refluxed for 16 hours under a nitrogenatmosphere and concentrated in vacuo. The residue was partitionedbetween dichloromethane (50 mL) and 1N aqueous hydrochloric acid (50mL). The organic phase was separated and washed twice with 1N aqueoushydrochloric acid (50 mL) then with 1N aqueous sodium hydroxide (50 mL).The resulting suspension was and filtered through filter agent and theorganic phase was separated and extracted sequentially with 1N aqueoussodium hydroxide (2×50 mL), water (50 mL), brine (50 mL), dried oversodium sulfate and concentrated in vacuo to give a thick pale yellowsyrup. This syrup was recrystallized from dichloromethane/hexane to give3.84 g (70%) of 2a as a pale yellow solid.

Step B.1-[2-(trimethylsilyl)ethoxy]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-benzo[b]furan]

Compound 2a (3.84 g, 10.7 mmol) was dissolved in absolute ethanol (82mL), water (2.6 mL), concentrated hydrochloric acid (1 mL) and combinedwith 10% palladium on carbon (2.67 g) in a Parr reaction vessel andshaken with 55 psi of hydrogen at room temperature for 16 hours. Theslurry was filtered through filter agent and the filtrate concentratedin vacuo to give 4.7 g (100%) of 2b as an off-white solid.

Step C. N-[(spiro[piperidine-4,3′-benzo[b]furan])-5′-methyl] carbamateWang resin

To a slurry of 4-nitrophenyl carbonate Wang resin (7.4 g, 1.3 mmol/g,9.7 mmol) in N,N-dimethylformamide (82 mL) was added 2b (4.7 g, 10.7mmol) in N,N-dimethylformamide (29 mL), N,N-diisopropylethylamine (3.19g, 24.9 mmol) and 4-dimethylaminopyridine (424 mg, 3.5 mmol). The slurrywas stirred overnight at room temperature under an argon atmosphere.After 16 hours, the resin was washed sequentially withN,N-dimethylformamide, methanol, N,N-dimethylformamide, methanol,dichloromethane, methanol, dichloromethane, methanol andtetrahydrofuran. The resin was added to tetrahydrofuran (62 mL) andtreated with 1M tetrabutylammonium fluoride in tetrahydrofuran (45 mL).After 16 hours, the resin was washed sequentially with tetrahydrofuran,methanol, tetrahydrofuran, methanol, dichloromethane, methanol,dichloromethane, methanol and dried on high vacuum to give Wangresin-bound compound 2c.

Step D. 5-phenylsulfanyl-furan-2-carboxylic acid methyl ester

To a solution of methyl 5-bromo-2-furoate (2.05 g, 10.0 mmol) inN,N-dimethylformamide (20 mL) was added benzenethiol sodium salt (1.58g, 12 mmol). The reaction mixture was heated to 75° C. for 3 hours, thencooled and diluted with ethyl acetate (20 mL) and water (20 mL). Theorganic layer was separated, extracted with water (3×20 mL), brine (20mL), dried over sodium sulfate and concentrated in vacuo to an ambersyrup. This syrup was purified via column chromatography on silica geleluting with hexane/ethyl acetate (7:3) to give 520 mg (22%) of 2d as acolorless liquid.

Step E. 5-phenylsulfanyl-furan-2-carboxylic acid

To a slurry of 2d (520 mg, 2.2 mmol) in tetrahydrofuran (2 mL), ethanol(2 mL), and water (2 mL) was added lithium hydroxide (98 mg, 2.3 mmol).The reaction mixture was stirred 16 hours at room temperature and thendiluted with ethyl acetate (5 mL) and water (5 mL). The organic layerwas separated, dried over sodium sulfate, filtered, and the filtrate wasconcentrated in vacuo to give 2e as a white solid (466 mg, 95%).

Step F.1-[(5-phenylthio)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-benzo[b]furan](Cpd 23)

Resin-bound compound 2c (585 mg, 0.45 mmol) in N,N-dimethylformamide (5mL) was combined with 2e (466 mg, 2.1 mmol), 1,3-diisopropylcarbodiimide(265 mg, 2.1 mmol), and 1-hydroxybenzotriazole (284 mg, 2.1 mmol), andthe mixture was shaken at room temperature for 16 hours. The resin wasisolated by filtration and extracted sequentially withN,N-dimethylformamide, methanol, N,N-dimethyl-formamide, methanol,dichloromethane, methanol, dichloromethane, methanol anddichloromethane. The resulting resin was treated with trifluoroaceticacid (5 mL) in dichloromethane (20 mL), shaken for 15 minutes, extractedwith dichloromethane (20 mL) and filtered. The filtrate was concentratedin vacuo and the residue was purified on a C18 reverse-phase column,eluting with water/acetonitrile (7:3) in the presence of 0.2%trifluoroacetic acid to give white powdered compound 23 (63 mg, 25%) asa trifluoroacetic acid salt: H¹ NMR (CD₃OD) δ 7.31-7.24 (m, 7H), 7.08(d, J=3.4 Hz, 1H), 6.84 (d, J=3.4 Hz, 1H), 6.81 (d, J=8.2 Hz, 1H), 4.53(s, 2H), 4.48-2.28 (br m, 2H), 4.03 (s, 2H), 3.32-3.08 (br m, 2H),2.03-1.79 (m, 4H); MS (ESI) m/z 420.8 (MH)⁺ for C₂₋₄H₂₄N₂O₃S.

Using the procedure of Example 2 and suitable reagents, startingmaterials and reaction conditions, other compounds representative of thepresent invention may be prepared:

Cpd Name 241-(3,4-dimethyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.32-7.15 (m, 5H), 6.82 (d, J = 8.2Hz, 1H), 4.56 (s, 3H), 4.04 (s, 2H), 3.80 (br m, 1H), 3.11 (br m, 2H),2.31 (s, 6H), 2.10-1.74 (m, 4H). C₂₂H₂₆N₂O₂; MS (ESI) m/z 350.9 (MH)⁺.25 1-(3-methyl-4-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.47 (d, J = 8.1 Hz, 1H), 7.39(d, J = 1.5 Hz, 1H), 7.30 (dd, J = 1.8 Hz, J = 13.0 Hz, 1H), 7.25 (s,1H), 7.22 (t, J = 6.3 Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H), 4.56 (s, 3H),4.04 (s, 2H), 3.74-3.71 (br m, 1H), 3.11-3.07 (br m, 2H), 2.42 (s, 3H),2.03-1.75 (m, 4H). C₂₁H₂₃ClN₂O₂; MS (ESI) m/z 370.8 (MH)⁺. 261-(3,4-difluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.46-7.22 (m, 5H), 6.82 (d, J = 8.2Hz, 1H), 4.56 (s, 3H), 4.04 (s, 2H), 3.88-3.55 (br m, 1H), 3.23-3.07 (brm, 2H), 1.93-1.88 (br m, 4H). C₂₀H₂₀F₂N₂O₂; MS (ESI) m/z 358.8 (MH)⁺. 271-(3-chloro-4-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.62 (dd, J = 2.0 Hz, J = 7.0Hz, 1H), 7.48-7.43 (m, 1H), 7.38 (d, J = 8.8 Hz, 1H), 7.33 (t, J = 1.9Hz, 1H), 7.24 (dd, J = 2.0 Hz, J = 8.2 Hz, 1H), 6.82 (d, J = 8.2 Hz,1H), 4.56 (br s, 3H), 4.05 (s, 2H), 3.93-3.43 (br m, 1H), 3.30-3.13 (brm, 2H), 2.03-1.76 (br m, 4H). C₂₀H₂₀ClFN₂O₂; MS (ESI) m/z 374.9 (MH)⁺.281-(3-chloro-4-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.51 (d, J = 2.0 Hz, 1H), 7.41(dd, J = 2.0 Hz, J = 8.4 Hz, 1H), 7.32 (d, J = 1.9 Hz, 1H), 7.23 (dd, J= 2.0 Hz, J = 8.2 Hz, 1H), 7.16 (d, J = 8.6 Hz, 1H), 6.82 (d, J = 8.2Hz, 1H), 4.56 (s, 3H), 4.05 (s, 2H), 3.94 (br s, 4H), 3.32-3.06 (br m,2H), 2.03-1.82 (br m, 4H). C₂₁H₂₃ClN₂O₃; MS (ESI) m/z 386.9 (MH)⁺. 291-(3-bromo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.68-7.63 (m, 2H), 7.54-7.38 (m, 2H),7.33 (d, J = 1.8 Hz, 1H), 7.23 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 6.82(d, J = 8.2 Hz, 1H), 4.56 (br s, 3H), 4.05 (s, 2H), 3.70-3.54 (br m,1H), 3.12-3.07 (br m, 2H), 2.03-1.76 (br m, 4H). C₂₀H₂₁BrN₂O₂; MS (ESI)m/z 400.8/ 401.8 (MH)⁺. 301-(3-methyl-4-bromo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.66 (d, J = 8.1 Hz, 1H), 7.38(d, J = 1.7 Hz, 1H), 7.32 (d, J = 1.9 Hz, 1H), 7.23 (dd, J = 1.9 Hz, J =8.2 Hz, 1H), 7.18 (dd, J = 2.0 Hz, J = 8.2 Hz, 1H), 6.82 (d, J = 8.2 Hz,1H), 4.56 (br s, 3H), 4.04 (s, 2H), 3.76 (br m, 1H), 3.12-3.07 (br m,2H), 2.44 (s, 3H), 2.03-1.75 (br m, 4H). C₂₁H₂₃BrN₂O₂; MS (ESI) m/z414.7/415.8 (MH)⁺. 311-(3-bromo-4-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.76 (dd, J = 2.0 Hz, J = 6.5Hz, 1H), 7.52-7.47 (m, 1H), 7.40-7.31 (m, 2H), 7.24 (dd, J = 2.0 Hz, J =8.2 Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H), 4.56 (br s, 3H), 4.05 (s, 2H),3.73 (br m, 1H), 3.14 (br m, 2H), 2.03-1.88 (br m, 4H). C₂₀H₂₀BrFN₂O₂;MS (ESI) m/z 419.7/ 420.8 (MH)⁺. 321-(3-bromo-4-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.67 (d, J = 2.1 Hz, 1H), 7.46(dd, J = 2.1 Hz, J = 8.5 Hz, 1H), 7.32 (d, J = 1.9 Hz, 1H), 7.23 (dd, J= 1.9 Hz, J = 8.2 Hz, 1H), 7.13 (d, J = 8.5 Hz, 1H), 6.82 (d, J = 8.2Hz, 1H), 4.56 (br s, 3H), 4.05 (s, 2H), 3.93 (s, 4H), 3.29-3.14 (br m,2H), 1.93-1.82 (br m, 4H). C₂₁H₂₃BrN₂O₃; MS (ESI) m/z 430.6/432.7 (MH)⁺.331-(3-nitro-4-bromo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 8.02 (d, J = 2.0 Hz, 1H), 7.96 (d,J = 8.2 Hz, 1H), 7.63 (dd, J = 2.0 Hz, J = 8.2 Hz, 1H), 7.33 (d, J = 1.8Hz, 1H), 7.24 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 6.82 (d, J = 8.2 Hz,1H), 4.56 (br s, 3H), 4.04 (s, 2H), 3.75-3.60 (br m, 1H), 3.25-3.05 (brm, 2H), 2.03-1.78 (br m, 4H). C₂₀H₂₀BrN₃O₄; MS (ESI) m/z 445.6/446.7(MH)⁺. 341-(3-iodo-4-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 8.00 (d, J = 1.9 Hz, 1H), 7.61 (d,J = 8.2 Hz, 1H), 7.46 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 7.33 (d, J = 1.8Hz, 1H), 7.24 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 6.82 (d, J = 8.2 Hz,1H), 4.55 (br s, 3H), 4.05 (s, 2H), 3.91-3.70 (br m, 1H), 3.25-3.05 (brm, 2H), 2.03-1.76 (br m, 4H). C₂₀H₂₀ClIN₂O₂; MS (ESI) m/z 482.7/484.6(MH)⁺. 36 1-phenylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.50-7.43 (m, 5H), 7.33 (d, J = 1.8 Hz,1H), 7.23 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H),4.55 (br s, 3H), 4.05 (s, 2H), 3.79-3.75 (br m, 1H), 3.25-3.05 (br m,2H), 2.03-1.74 (br m, 4H). C₂₀H₂₂N₂O₂; MS (ESI) m/z 323.0 (MH)⁺. 371-cyclohexylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.27 (d, J = 1.7 Hz, 1H), 7.22 (dd, J =1.9 Hz, J = 8.2 Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H), 4.57-4.46 (m, 3H),4.08-4.03 (m, 3H), 2.90-2.81 (m, 1H), 2.73-2.66 (m, 1H), 1.88-1.74 (m,8H), 1.56-1.24 (m, 7H). C₂₀H₂₈N₂O₂; MS (ESI) m/z 329.0 (MH)⁺. 381-(trans-4-methyl-cyclohexyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.26 (d, J = 1.7 Hz, 1H), 7.22(dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H), 4.58-4.47(m, 3H), 4.07-4.03 (m, 3H), 3.29 (m, 1H), 2.90-2.80 (m, 1H), 2.67-2.60(m, 1H), 1.88-1.75 (m, 8H), 1.61-1.35 (m, 3H), 1.10-0.98 (m, 2H), 0.92(d, J = 6.5 Hz, 3H). C₂₁H₃₀N₂O₂; MS (ESI) m/z 342.9 (MH)⁺. 391-(3-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.53-7.45 (m, 3H), 7.40-7.37 (m, 1H),7.33 (d, J = 1.9 Hz, 1H), 7.23 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 6.82(d, J = 8.2 Hz, 1H), 4.56 (br s, 3H), 4.05 (s, 2H), 3.80-3.65 (br m,1H), 3.17-3.07 (br m, 2H), 2.03-1.76 (br m, 4H). C₂₀H₂₁ClN₂O₂; MS (ESI)m/z 356.9/ 358.8 (MH)⁺. 401-(3,4-dimethoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.32 (d, J = 1.7 Hz, 1H), 7.23 (dd,J = 1.9 Hz, J = 8.2 Hz, 1H), 7.08-7.01 (m, 3H), 6.82 (d, J = 8.2 Hz,1H), 4.57 (s, 2H), 4.04 (s, 2H), 3.87 (s, 6H), 3.80-3.65 (br m, 2H),3.17-3.07 (br m, 2H), 2.03-1.76 (br m, 4H). C₂₂H₂₆N₂O₄; MS (ESI) m/z382.8 (MH)⁺. 411-(3-methyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.38-7.30 (m, 4H), 7.26 (s, 1H), 7.23(dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H), 4.56 (br s,3H), 4.05 (s, 2H), 3.85-3.75 (br m, 1H), 3.17-3.07 (br m, 2H), 2.39 (s,3H), 1.98-1.74 (br m, 4H). C₂₁H₂₄N₂O₂; MS (ESI) m/z 336.9 (MH)⁺. 421-(3-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.55-7.48 (m, 1H), 7.33-7.21 (m, 5H),6.82 (d, J = 8.2 Hz, 1H), 4.56 (br s, 3H), 4.05 (s, 2H), 3.80-3.65 (brm, 1H), 3.17-3.07 (br m, 2H), 2.03-1.76 (br m, 4H). C₂₀H₂₁FN₂O₂; MS(ESI) m/z 340.8 (MH)⁺. 431-(4-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.54-7.49 (m, 2H), 7.31 (d, J = 1.8 Hz,1H), 7.25-7.19 (m, 3H), 6.82 (d, J = 8.2 Hz, 1H), 4.56 (br s, 3H), 4.04(s, 2H), 3.80-3.65 (br m, 1H), 3.17-3.07 (br m, 2H), 2.03-1.68 (br m,4H). C₂₀H₂₁FN₂O₂; MS (ESI) m/z 340.8 (MH)⁺. 441-(4-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.52-7.44 (m, 4H), 7.32 (d, J = 1.9 Hz,1H), 7.23 (dd, J = 2.0 Hz, J = 8.2 Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H),4.56 (br s, 3H), 4.04 (s, 2H), 3.80-3.65 (br m, 1H), 3.17-3.07 (br m,2H), 1.98-1.77 (br m, 4H). C₂₀H₂₁ClN₂O₂; MS (ESI) m/z 356.9/358.8 (MH)⁺.45 1-(4-methylthio-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.41-7.31 (m, 5H), 7.23 (dd, J =2.0 Hz, J = 8.2 Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H), 4.56 (br s, 3H), 4.04(s, 2H), 3.95-3.75 (br m, 1H), 3.17-3.07 (br m, 2H), 2.51 (s, 3H),2.03-1.86 (br m, 4H). C₂₁H₂₄N₂O₂S; MS (ESI) m/z 368.9 (MH)⁺. 461-(3-fluoro-4-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.61 (t, J = 8.0 Hz, 1H),7.40-7.22 (m, 4H), 6.82 (d, J = 8.2 Hz, 1H), 4.56 (br s, 3H), 4.04 (s,2H), 3.85-3.65 (br m, 1H), 3.17-3.07 (br m, 2H), 2.03-1.86 (br m, 4H).C₂₀H₂₀ClFN₂O₂; MS (ESI) m/z 374.9/376.8 (MH)⁺. 471-(3-trifluoromethyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.83-7.67 (m, 4H), 7.33 (d, J = 1.8Hz, 1H), 7.23 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 6.82 (d, J = 8.2 Hz,1H), 4.56 (br s, 3H), 4.04 (s, 2H), 3.85-3.65 (br m, 1H), 3.17-3.07 (brm, 2H), 2.03-1.86 (br m, 4H). C₂₁H₂₁F₃N₂O₂; MS (ESI) m/z 390.8 (MH)⁺. 481-(3-iodo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.78-7.72 (m, 2H), 7.47-7.35 (m, 2H),),7.19-7.12 (m, 2H), 6.73 (d, J = 8.2 Hz, 1H), 4.46 (br s, 3H), 3.95 (s,2H), 3.85-3.65 (br m, 1H), 3.17-3.07 (br m, 2H), 2.03-1.86 (br m, 4H).C₂₀H₂₁IN₂O₂; MS (ESI) m/z 448.6 (MH)⁺. 491-(4-iodo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.86 (dd, J = 1.7 Hz, J = 6.6 Hz, 2H),7.31 (d, J = 1.9 Hz, 1H), 7.25-7.21 (m, 3H), 6.82 (d, J = 8.2 Hz, 1H),4.56 (br s, 3H), 4.04 (s, 2H), 3.85-3.65 (br m, 1H), 3.17-3.07 (br m,2H), 2.03-1.76 (br m, 4H). C₂₀H₂₁IN₂O₂; MS (ESI) m/z 448.6 (MH)⁺. 501-(3-iodo-4-methyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.90 (d, J = 1.2 Hz, 1H), 7.41-7.35(m, 2H), 7.32 (d, J = 1.9 Hz, 1H), 7.23 (dd, J = 1.9 Hz, J = 8.2 Hz,1H), 6.82 (d, J = 8.2 Hz, 1H), 4.56 (br s, 3H), 4.04 (s, 2H), 3.85-3.65(br m, 1H), 3.17-3.07 (br m, 2H), 2.47 (s, 3H), 2.03-1.77 (br m, 4H).C₂₁H₂₃IN₂O₂; MS (ESI) m/z 462.6 (MH)⁺. 511-(3-methyl-4-iodo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.94 (d, J = 8.0 Hz, 1H), 7.36 (d,J = 1.9 Hz, 1H), 7.32 (d, J = 1.9 Hz, 1H), 7.23 (dd, J = 1.9 Hz, J = 8.2Hz, 1H), 6.99 (dd, J = 1.8 Hz, J = 8.0 Hz, 1H), 6.82 (d, J = 8.2 Hz,1H), 4.55 (br s, 3H), 4.04 (s, 2H), 3.85-3.65 (br m, 1H), 3.17-3.07 (brm, 2H), 2.47 (s, 3H), 2.03-1.74 (br m, 4H). C₂₁H₂₃IN₂O₂; MS (ESI) m/z462.6 (MH)⁺. 521-(3-iodo-4-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.89 (d, J = 2.1 Hz, 1H), 7.48(dd, J = 2.1 Hz, J = 8.5 Hz, 1H), 7.32 (d, J = 1.8 Hz, 1H), 7.23 (dd, J= 1.9 Hz, J = 8.2 Hz, 1H), 7.03 (d, J = 8.5 Hz, 1H), 6.82 (d, J = 8.2Hz, 1H), 4.56 (br s, 3H), 4.04 (s, 2H), 3.92 (s, 3H), 3.85-3.65 (br m,1H), 3.17-3.07 (br m, 2H), 1.99-1.82 (br m, 4H). C₂₁H₂₃IN₂O₃; MS (ESI)m/z 478.6 (MH)⁺. 531-(3-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.42-7.34 (m, 2H), 7.23 (d, J = 8.2 Hz,1H), 7.07-7.00 (m, 3H), 6.82 (d, J = 8.2 Hz, 1H), 4.56 (br s, 3H), 4.04(s, 2H), 3.84 (s, 3H), 3.80-3.65 (br m, 1H), 3.17-3.07 (br m, 2H),1.99-1.82 (br m, 4H). C₂₁H₂₄N₂O₃; MS (ESI) m/z 352.8 (MH)⁺. 541-(4-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.45-7.32 (m, 2H), 7.24 (d, J = 1.9 Hz,1H), 7.21 (d, J = 1.9 Hz, 1H), 7.03-6.98 (m, 2H), 6.82 (d, J = 8.2 Hz,1H), 4.56 (br s, 3H), 4.04 (s, 2H), 3.84 (s, 3H), 3.80-3.65 (br m, 1H),3.17-3.07 (br m, 2H), 1.99-1.82 (br m, 4H). C₂₁H₂₄N₂O₃; MS (ESI) m/z352.8 (MH)⁺. 551-(4-dimethylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.44-7.39 (m, 2H), 7.32 (d, J= 1.8 Hz, 1H), 7.23 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 6.98-6.90 (m, 2H),6.82 (d, J = 8.2 Hz, 1H), 4.56 (br s, 2H), 4.40-4.10 (br m, 1H), 4.04(s, 2H), 3.17-3.07 (br m, 3H), 3.07 (s, 6H), 1.99-1.82 (br m, 4H).C₂₂H₂₇N₃O₂; MS (ESI) m/z 365.9 (MH)⁺. 561-(3-dimethylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.51-7.11 (m, 6H), 6.82 (d, J= 8.2 Hz, 1H), 4.56 (br s, 3H), 4.04 (s, 2H), 3.80-3.70 (br m, 1H),3.17-3.07 (br m, 2H), 3.13 (s, 6H), 1.99-1.82 (br m, 4H). C₂₂H₂₇N₃O₂; MS(ESI) m/z 365.9 (MH)⁺. 571-(3-methylthio-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.43-7.36 (m, 2H), 7.33-7.31 (m,2H), 7.25-7.18 (m, 2H), 6.82 (d, J = 8.2 Hz, 1H), 4.56 (br s, 3H), 4.04(s, 2H), 3.85-3.75 (br m, 1H), 3.17-3.07 (br m, 2H), 2.51 (s, 3H),2.00-1.75 (br m, 4H). C₂₁H₂₄N₂O₂S; MS (ESI) m/z 368.9 (MH)⁺. 581-(4-methoxycarbonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 8.14-8.11 (m, 2H), 7.58-7.55(m, 2H), 7.34 (d, J = 1.8 Hz, 1H), 7.23 (dd, J = 1.9 Hz, J = 8.2 Hz,1H), 6.82 (d, J = 8.2 Hz, 1H), 4.55 (br s, 3H), 4.05 (s, 2H), 3.93 (s,3H), 3.75-3.65 (br m, 1H), 3.17-3.07 (br m, 2H), 2.03-1.70 (br m, 4H).C₂₂H₂₄N₂O₄; MS (ESI) m/z 380.9 (MH)⁺. 591-(4-bromo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.70-7.66 (m, 2H), 7.43-7.40 (m, 2H),7.35 (s, 1H), 7.26 (d, J = 8.2 Hz, 1H), 6.84 (dd, J = 1.3 Hz, J = 8.2Hz, 1H), 4.55 (br s, 3H), 4.05 (s, 2H), 3.75-3.65 (br m, 1H), 3.17-3.07(br m, 2H), 2.03-1.70 (br m, 4H). C₂₀H₂₁BrN₂O₂; MS (ESI) m/z 400.6/402.7(MH)⁺. 601-(3-trifluoromethoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.60 (t, J = 7.9 Hz, 1H),7.48-7.39 (m, 3H), 7.34 (d, J = 1.8 Hz, 1H), 7.23 (dd, J = 1.9 Hz, J =8.2 Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H), 4.56 (br s, 3H), 4.05 (s, 2H),3.75-3.65 (br m, 1H), 3.17-3.07 (br m, 2H), 2.01-1.76 (br m, 4H).C₂₁H₂₁F₃N₂O₃; MS (ESI) m/z 406.8 (MH)⁺. 611-(4-trifluoromethoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.58 (d, J = 8.5 Hz, 2H), 7.40(d, J = 8.6 Hz, 2H), 7.31 (s, 1H), 7.23 (d, J = 8.3 Hz, 1H), 6.82 (d, J= 8.3 Hz, 1H), 4.56 (br s, 3H), 4.05 (s, 2H), 3.75-3.65 (br m, 1H),3.17-3.07 (br m, 2H), 2.01-1.76 (br m, 4H). C₂₁H₂₁F₃N₂O₃; MS (ESI) m/z406.8 (MH)⁺. 621-(4-phenoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.49-7.37 (m, 4H), 7.32 (d, J = 1.9 Hz,1H), 7.25-7.16 (m, 2H), 7.07-7.03 (m, 4H), 6.82 (d, J = 8.2 Hz, 1H),4.56 (br s, 3H), 4.05 (s, 2H), 3.75-3.65 (br m, 1H), 3.17-3.07 (br m,2H), 1.93-1.83 (br m, 4H). C₂₆H₂₆N₂O₃; MS (ESI) m/z 414.8 (MH)⁺. 631-(3-trifluoromethylthio-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.83 (dd, J = 1.9 Hz, J = 6.8Hz, 1H), 7.79 (s, 1H), 7.68-7.60 (m, 2H), 7.33 (d, J = 1.9 Hz, 1H), 7.23(dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H), 4.56 (br s,3H), 4.05 (s, 2H), 3.75-3.65 (br m, 1H), 3.17-3.07 (br m, 2H), 2.01-1.76(br m, 4H). C₂₁H₂₁F₃N₂O₂S; MS (ESI) m/z 422.7 (MH)⁺. 641-[3-(4-methoxy-phenyl)-phenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.72 (m, 5H),7.37 (dd, J = 1.3 Hz, J = 6.3 Hz, 1H), 7.33 (d, J = 1.8 Hz, 1H), 7.23(dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 7.05-7.00 (m, 2H), 6.82 (d, J = 8.2Hz, 1H), 4.57 (br s, 3H), 4.04 (s, 2H), 3.84 (br s, 4H), 3.17-3.07 (brm, 2H), 2.02-1.76 (br m, 4H). C₂₇H₂₈N₂O₃; MS (ESI) m/z 428.9 (MH)⁺. 661-(3-cyano-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.88-7.85 (m, 2H), 7.78-7.75 (m, 1H),7.70-7.65 (m, 1H), 7.33 (d, J = 1.8 Hz, 1H), 7.23 (dd, J = 2.0 Hz, J =8.2 Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H), 4.56 (br s, 3H), 4.05 (s, 2H),3.75-3.60 (br m, 1H), 3.17-3.07 (br m, 2H), 2.09-1.76 (br m, 4H).C₂₁H₂₁N₃O₂; MS (ESI) m/z 347.9 (MH)⁺. 671-(4-methylcarbonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 8.09 (dd, J = 1.7 Hz, J = 6.8Hz, 2H), 7.58 (dd, J = 1.7 Hz, J = 6.8 Hz, 2H), 7.34 (d, J = 1.7 Hz,1H), 7.24 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H),4.56 (br s, 3H), 4.05 (s, 2H), 3.80-3.65 (br m, 1H), 3.17-3.07 (br m,2H), 2.64 (s, 3H), 2.06-1.70 (br m, 4H). C₂₂H₂₄N₂O₃; MS (ESI) m/z 364.8(MH)⁺. 681-benzodioxol-5-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.32 (d, J = 1.5 Hz, 1H), 7.22 (dd, J =1.9 Hz, J = 8.2 Hz, 1H), 7.00-6.89 (m, 3H), 6.82 (d, J = 8.2 Hz, 1H),6.02 (s, 2H), 4.56 (br s, 3H), 4.04 (s, 2H), 4.0-3.70 (br m, 1H),3.40-3.15 (br m, 2H), 1.93-1.81 (br m, 4H). C₂₁H₂₂N₂O₄; MS (ESI) m/z366.8 (MH)⁺. 691-(4-chloromethyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.56-7.45 (m, 2H), 7.40-7.37 (m,2H), 7.32 (d, J = 1.8 Hz, 1H), 7.23 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H),6.82 (d, J = 8.2 Hz, 1H), 4.69 (s, 2H), 4.56 (br s, 3H), 4.05 (s, 2H),3.85-3.65 (br m, 1H), 3.20-3.05 (br m, 2H), 2.03-1.75 (br m, 4H).C₂₁H₂₃ClN₂O₂; MS (ESI) m/z 370.8/372.8 (MH)⁺. 701-naphthalen-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 8.00-7.92 (m, 4H), 7.61-7.52 (m, 3H),7.35 (d, J = 1.8 Hz, 1H), 7.23 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 6.82(d, J = 8.2 Hz, 1H), 4.70-4.60 (br m, 1H), 4.56 (s, 2H), 4.05 (s, 2H),3.90-3.75 (br m, 1H), 3.25-3.10 (br m, 2H), 2.03-1.76 (br m, 4H).C₂₄H₂₄N₂O₂; MS (ESI) m/z 372.9 (MH)⁺. 711-(4-trifluoromethyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.32 (d, J = 8.2 Hz, 2H), 7.65 (d,J = 8.1 Hz, 2H), 7.32 (d, J = 1.8 Hz, 1H), 7.23 (dd, J = 1.9 Hz, J = 8.2Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H), 4.57 (br s, 3H), 4.04 (s, 2H),3.75-3.65 (br m, 1H), 3.20-3.05 (br m, 2H), 2.03-1.75 (br m, 4H).C₂₁H₂₁F₃N₂O₂; MS (ESI) m/z 390.9 (MH)⁺. 721-(3-methylsulfonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 8.11-8.07 (m, 1H), 8.04 (d, J= 1.5 Hz, 1H), 7.83-7.74 (m, 2H), 7.34 (d, J = 1.8 Hz, 1H), 7.23 (dd, J= 1.9 Hz, J = 8.2 Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H), 4.57 (br s, 3H),4.05 (s, 2H), 3.75-3.65 (br m, 1H), 3.17 (br s, 5H), 2.03-1.73 (br m,4H). C₂₁H₂₄N₂O₄S; MS (ESI) m/z 400.8 (MH)⁺. 731-(4-cyclohexyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.40-7.31 (m, 5H), 7.23 (dd, J =1.9 Hz, J = 8.2 Hz, 1H), 6.81 (d, J = 8.2 Hz, 1H), 4.55 (br s, 3H), 4.04(s, 2H), 3.95-3.75 (br m, 1H), 3.25-3.15 (br m, 2H), 2.65-2.50 (br m,1H), 2.10-1.60 (br m, 9H), 1.50-1.20 (br m, 5H). C₂₆H₃₂N₂O₂; MS (ESI)m/z 404.9 (MH)⁺. 741-(3-trifluoromethyl-4-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.83-7.77 (m,2H), 7.51-7.44 (m, 1H), 7.33 (d, J = 1.9 Hz, 1H), 7.23 (dd, J = 1.9 Hz,J = 8.2 Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H), 4.56 (br s, 3H), 4.04 (s,2H), 3.80-3.60 (br m, 1H), 3.25-3.05 (br m, 2H), 2.10-1.65 (br m, 4H).C₂₁H₂₀F₄N₂O₂; MS (ESI) m/z 408.8 (MH)⁺. 751-(4-benzyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.41-7.15 (m, 11H), 6.82 (d, J = 8.2 Hz,1H), 4.56 (br s, 3H), 4.06 (s, 2H), 4.04 (s, 2H), 3.85-3.70 (br m, 1H),3.25-3.05 (br m, 2H), 2.10-1.65 (br m, 4H). C₂₇H₂₈N₂O₂; MS (ESI) m/z413.2 (MH)⁺. 761-(4-benzyloxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.46-7.31 (m, 8H), 7.23 (dd, J =1.9 Hz, J = 8.2 Hz, 1H), 7.10-7.07 (m, 2H), 6.82 (d, J = 8.2 Hz, 1H),5.15 (s, 2H), 4.56 (br s, 3H), 4.04 (s, 2H), 3.95-3.70 (br m, 1H),3.25-3.10 (br m, 2H), 2.05-1.65 (br m, 4H). C₂₇H₂₈N₂O₃; MS (ESI) m/z429.2 (MH)⁺. 781-benzylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.28-7.10 (m, 5H), 7.06 (d, J = 1.8 Hz,1H), 6.70 (d, J = 6.2 Hz, 1H), 4.50-4.42 (m, 1H), 4.39 (s, 2H),4.00-3.95 (m, 1H), 3.92 (s, 2H), 3.74 (s, 2H), 3.18-3.09 (m, 1H),2.86-2.76 (m, 1H), 3.25-3.10 (br m, 1H), 1.77-1.51 (m, 4H). C₂₁H₂₄N₂O₂;MS (ESI) m/z 337.2 (MH)⁺. 791-phenethylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.35-7.21 (m, 7H), 6.83 (d, J = 8.0 Hz,1H), 4.50 (br s, 3H), 4.05 (s, 2H), 3.92 (br d, J = 13.9 Hz, 1H),3.34-3.14 (m, 1H), 3.00-2.73 (m, 5H), 1.80-1.62 (m, 4H). C₂₂H₂₆N₂O₂; MS(ESI) m/z 351.1 (MH)⁺. 801-(3-fluoro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.42-7.34 (m, 1H), 7.26-7.20 (m, 2H),7.14-7.00 (m, 3H), 6.83 (d, J = 8.1 Hz, 1H), 4.52 (br s, 3H), 4.04 (brs, 3H), 3.87 (s, 2H), 3.34-3.24 (m, 1H), 2.99-2.89 (m, 1H), 2.05-1.70(m, 4H). C₂₁H₂₃FN₂O₂; MS (ESI) m/z 355.2 (MH)⁺. 811-(3-chloro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.36-7.18 (m, 6H), 6.81 (d, J = 8.1 Hz,1H), 4.51 (br s, 3H), 4.02 (br s, 3H), 3.84 (s, 2H), 3.00-2.87 (m, 1H),2.76-2.03 (br m, 1H), 2.03-1.66 (m, 4H). C₂₁H₂₃ClN₂O₂; MS (ESI) m/z371.2/373.2 (MH)⁺. 821-(3,4-difluoro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.18-7.11 (m, 4H), 7.09-6.97 (br m,1H), 6.72 (d, J = 8.1 Hz, 1H), 4.42 (s, 2H), 4.41-4.37 (m, 1H),3.99-3.95 (br m, 1H), 3.93 (s, 2H), 3.73 (s, 2H), 3.24-3.14 (m, 1H),2.87-2.77 (m, 1H), 1.80-1.60 (m, 4H). C₂₁H₂₂F₂N₂O₂; MS (ESI) m/z 373.2(MH)⁺. 831-(3-chloro-phenethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.32-7.19 (m, 6H), 6.81 (d, J = 8.1Hz, 1H), 4.49 (s, 2H), 4.48-4.44 (m, 1H), 4.04 (s, 2H), 3.92 (br d, J =13.8 Hz, 1H), 3.24-3.15 (m, 1H), 2.98-2.70 (m, 5H), 1.78-1.62 (m, 4H).C₂₂H₂₅ClN₂O₂; MS (ESI) m/z 385.2 (MH)⁺. 841-naphthalen-2-ylmethylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.81-7.68 (m, 4H), 7.42-7.34 (m,3H), 7.09 (d, J = 8.1 Hz, 1H), 6.94 (s, 1H), 6.68 (d, J = 8.3 Hz, 1H),4.50-4.41 (m, 1H), 4.39 (s, 2H), 4.01-3.97 (m, 1H), 3.91 (s, 2H), 3.86(s, 2H), 3.21-3.12 (m, 1H), 2.89-2.78 (m, 1H), 1.77-1.63 (m, 2H),1.57-1.42 (m, 2H). C₂₅H₂₆N₂O₂; MS (ESI) m/z 387.2 (MH)⁺. 851-(3-trifluoromethyl-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.61-7.51 (m, 4H), 7.30-7.18 (m,2H), 6.81 (d, J = 8.1 Hz, 1H), 4.52 (s, 2H), 4.51-4.47 (m, 1H),4.15-4.07 (m, 1H), 4.02 (s, 2H), 3.94 (s, 2H), 3.34-3.25 (m, 1H),3.07-2.72 (m, 1H), 1.85-1.71 (m, 4H). C₂₂H₂₃F₃N₂O₂; MS (ESI) m/z 405.1(MH)⁺. 861-(3,4-dichloro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.41-7.38 (m, 2H), 7.14-7.11 (m,3H), 6.71 (d, J = 8.0 Hz, 1H), 4.42 (s, 2H), 4.41-4.36 (m, 1H), 3.93 (brs, 3H), 3.74 (s, 2H), 3.24-3.14 (m, 1H), 2.87-2.77 (m, 1H), 1.84-1.64(m, 4H). C₂₁H₂₂Cl₂N₂O₂; MS (ESI) m/z 405.1/407.1 (MH)⁺. 871-(3-bromo-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.40 (s, 1H), 7.36-7.32 (m, 1H),7.19-7.09 (m, 4H), 6.71 (d, J = 8.1 Hz, 1H), 4.41 (s, 2H), 4.40-4.38 (m,1H), 3.93 (s, 2H), 3.92-3.89 (m, 1H), 3.74 (s, 2H), 3.22-3.12 (m, 1H),2.86-2.65 (m, 1H), 1.79-1.56 (m, 4H). C₂₁H₂₃BrN₂O₂; MS (ESI) m/z415.1/417.1 (MH)⁺. 881-(3-phenoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.28-7.26 (m, 3H), 7.25-6.86 (m, 6H),6.85 (d, J = 1.9 Hz, 1H), 6.78 (dd, J = 2.0 Hz, J = 8.2 Hz, 1H), 6.71(d, J = 8.1 Hz, 1H), 4.39 (s, 2H), 4.38-4.35 (m, 1H), 3.90 (br s, 3H),3.72 (s, 2H), 3.20-3.10 (m, 1H), 2.85-2.76 (m, 1H), 1.78-1.57 (m, 4H).C₂₇H₂₈N₂O₃; MS (ESI) m/z 429.3 (MH)⁺. 891-(3-methyl-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.15-6.97 (m, 6H), 6.70 (d, J = 8.2 Hz,1H), 4.39 (br s, 3H), 3.92 (br s, 3H), 3.69 (s, 2H), 3.20-3.08 (m, 1H),2.86-2.76 (m, 1H), 2.24 (s, 3H), 1.77-1.59 (m, 2H), 1.56-1.52 (m, 2H).C₂₂H₂₆N₂O₂; MS (ESI) m/z 351.3 (MH)⁺. 901-(4-fluoro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.23-7.18 (m, 2H), 7.14-7.08 (m, 2H),7.02-6.95 (m, 2H), 6.71 (d, J = 8.2 Hz, 1H), 4.41 (br s, 3H), 3.92 (brs, 3H), 3.72 (s, 2H), 3.22-3.12 (m, 1H), 2.86-2.76 (m, 1H), 1.78-1.57(m, 4H). C₂₁H₂₃FN₂O₂; MS (ESI) m/z 355.2 (MH)⁺. 911-(4-chloro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.27-7.08 (m, 6H), 6.71 (d, J = 8.1 Hz,1H), 4.41 (br s, 3H), 3.93 (br s, 3H), 3.72 (s, 2H), 3.21-3.12 (m, 1H),2.86-2.76 (m, 1H), 1.78-1.57 (m, 4H). C₂₁H₂₃ClN₂O₂; MS (ESI) m/z 371.2(MH)⁺. 921-(4-phenyl-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.64-7.60 (m, 4H), 7.46-7.30 (m, 5H),7.19 (dd, J = 1.9 Hz, J = 8.1 Hz, 1H), 7.14 (d, J = 1.8 Hz, 1H), 6.80(d, J = 8.2 Hz, 1H), 4.53-4.51 (m, 1H), 4.50 (s, 2H), 4.06 (br d, J =14.5 Hz, 1H), 3.95 (d, J = 2.9 Hz, 2H), 3.88 (s, 2H), 3.31-3.22 (m, 1H),2.97-2.87 (m, 1H), 1.87-1.58 (m, 4H). C₂₇H₂₈N₂O₂; MS (ESI) m/z 413.3(MH)⁺. 931-(4-bromo-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.52-7.48 (m, 2H), 7.24-7.17 (m, 4H),6.80 (d, J = 8.2 Hz, 1H), 4.50 (s, 2H), 4.49-4.46 (m, 1H), 4.02 (s, 2H),4.01-3.98 (m, 1H), 3.80 (s, 2H), 3.32-3.18 (m, 1H), 2.96-2.86 (m, 1H),1.86-1.62 (m, 4H). C₂₁H₂₃BrN₂O₂; MS (ESI) m/z 415.2/417.1 (MH)⁺. 941-(4-methoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.34-7.07 (m, 7H), 7.00-6.94 (m, 4H),6.80 (d, J = 8.2 Hz, 1H), 4.51 (br s, 3H), 4.10-4.06 (m, 1H), 3.99 (s,2H), 3.82 (s, 2H), 3.32-3.22 (m, 1H), 2.96-2.86 (m, 1H), 1.89-1.60 (m,4H). C₂₇H₂₈N₂O₃; MS (ESI) m/z 429.3 (MH)⁺. 951-(3-bromo-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.46 (s, 1H), 7.40-7.36 (m, 1H),7.27-7.20 (m, 4H), 6.80 (d, J = 8.2 Hz, 1H), 4.49 (s, 2H), 4.48-4.44 (m,1H), 4.04 (s, 2H), 3.91 (br d, J = 14.2 Hz, 1H), 3.24-3.15 (m, 1H),2.97-2.67 (m, 5H), 1.78-1.60 (m, 4H). C₂₂H₂₅BrN₂O₂; MS (ESI) m/z429.1/431.2 (MH)⁺. 961-(4-iodo-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.72-7.68 (m, 2H), 7.21 (dd, J = 2.0 Hz,J = 8.2 Hz, 1H), 7.16 (d, J = 1.8 Hz, 1H), 7.10 (s, 1H), 7.08 (s, 1H),6.80 (d, J = 8.2 Hz, 1H), 4.50 (s, 2H), 4.49-4.46 (m, 1H), 4.03 (s, 2H),4.02-3.97 (m, 1H), 3.79 (s, 2H), 3.32-3.20 (m, 1H), 2.95-2.86 (m, 1H),1.82-1.64 (m, 4H). C₂₁H₂₃IN₂O₂; MS (ESI) m/z 463.2 (MH)⁺. 971-(3-iodo-phenethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.65 (d, J = 1.5 Hz, 1H), 7.58 (d, J =7.9 Hz, 1H), 7.30-7.22 (m, 3H), 7.08 (t, J = 7.8 Hz, 1H), 6.80 (d, J =8.8 Hz, 1H), 4.49 (s, 2H), 4.48-4.43 (m, 1H), 4.05 (s, 2H), 3.90 (br d,J = 14.0 Hz, 1H), 3.23-3.13 (m, 1H), 2.94-2.68 (m, 5H), 1.78-1.60 (m,4H). C₂₂H₂₅IN₂O₂; MS (ESI) m/z 477.1 (MH)⁺. 981-(3-methyl-phenethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.24-7.16 (m, 3H), 7.08-7.02 (m,3H), 6.81 (d, J = 8.1 Hz, 1H), 4.48 (s, 2H), 4.47-4.45 (m, 1H), 4.03 (s,2H), 3.90 (br d, J = 14.5 Hz, 1H), 3.22-3.12 (m, 1H), 2.93-2.82 (m, 3H),2.75-2.69 (m, 2H), 2.31 (m, 3H), 1.78-1.62 (m, 4H). C₂₃H₂₈N₂O₂; MS (ESI)m/z 365.2 (MH)⁺. 991-(3-methoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.32-7.23 (m, 2H), 7.18 (d, J = 1.6 Hz,1H), 6.91-6.82 (m, 4H), 4.55-4.53 (m, 1H), 4.52 (s, 2H), 4.05 (s, 2H),4.04-4.02 (m, 1H), 3.84 (s, 2H), 3.83 (s, 3H), 3.30-3.22 (m, 1H),2.99-2.89 (m, 1H), 1.86-1.81 (m, 2H), 1.69-1.65 (m, 2H). C₂₂H₂₆N₂O₃; MS(ESI) m/z 367.2 (MH)⁺. 1001-benzodioxol-5-ylmethylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.23-7.18 (m, 2H), 6.82-6.73 (m,4H), 5.93 (d, J = 1.7 Hz, 2H), 4.50 (s, 2H), 4.49-4.46 (m, 1H), 4.02 (brs, 3H), 3.74 (s, 2H), 3.30-3.20 (m, 1H), 2.95-2.85 (m, 1H), 1.90-1.65(m, 4H). C₂₂H₂₄N₂O₄; MS (ESI) m/z 381.3 (MH)⁺. 1011-(3-methoxy-phenethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.24-7.18 (m, 3H), 6.85-6.76 (m,4H), 4.48 (s, 2H), 4.47-4.44 (m, 1H), 4.04 (s, 2H), 3.90 (br d, J = 14.0Hz, 1H), 3.79 (s, 3H), 3.22-3.12 (m, 1H), 2.95-2.68 (m, 5H), 1.77-1.51(m, 4H). C₂₃H₂₈N₂O₃; MS (ESI) m/z 381.3 (MH)⁺. 1021-(3-methyl-4-methoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.21 (dd, J = 1.9 Hz, J = 8.2Hz, 1H), 7.15 (d, J = 1.8 Hz, 1H), 7.08-7.05 (m, 2H), 6.86 (d, J = 8.2Hz, 1H), 6.80 (d, J = 8.2 Hz, 1H), 4.48 (br s, 3H), 4.01 (br s, 3H),3.81 (s, 3H), 3.72 (s, 2H), 3.23-3.17 (m, 1H), 2.95-2.85 (m, 1H), 2.18(s, 3H), 1.82-1.61 (m, 4H). C₂₃H₂₈N₂O₃; MS (ESI) m/z 381.3 (MH)⁺. 1031-(3-methylthio-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.28-7.20 (m, 5H), 7.14 (d, J = 1.8Hz, 1H), 6.80 (d, J = 8.2 Hz, 1H), 4.49 (br s, 3H), 4.02 (s, 2H),4.01-3.98 (m, 1H), 3.79 (s, 2H), 3.23-3.19 (m, 1H), 2.95-2.85 (m, 1H),2.46 (s, 3H), 1.81-1.60 (m, 4H). C₂₂H₂₆N₂O₂S; MS (ESI) m/z 383.3 (MH)⁺.1041-(benzodioxol-5-ylethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.22 (dd, J = 1.9 Hz, J = 8.2 Hz,1H), 7.17 (d, J = 1.8 Hz, 1H), 6.82-6.69 (m, 4H), 5.90-5.87 (m, 2H),4.49 (s, 2H), 4.48-4.46 (m, 1H), 4.04 (s, 2H), 3.91 (br d, J = 14.7 Hz,1H), 3.23-3.14 (m, 1H), 2.90-2.60 (m, 5H), 1.76-1.51 (m, 4H).C₂₃H₂₆N₂O₄; MS (ESI) m/z 395.2 (MH)⁺. 1051-(3,4-dimethoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.21 (dd, J = 1.9 Hz, J = 8.2 Hz,1H), 7.10 (d, J = 1.8 Hz, 1H), 6.94-6.92 (m, 2H), 6.86-6.78 (m, 2H),4.49 (br s, 3H), 4.02 (br s, 3H), 3.84 (s, 3H), 3.82 (s, 3H), 3.77 (s,2H), 3.24-3.19 (m, 1H), 2.94-2.84 (m, 1H), 1.80-1.53 (m, 4H).C₂₃H₂₈N₂O₄; MS (ESI) m/z 397.2 (MH)⁺. 1061-(3-methoxy-4-benzyloxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.43-7.26 (m,5H), 7.21 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 7.11 (d, J = 1.8 Hz, 1H),6.97-6.94 (m, 2H), 6.82-6.79 (m, 2H), 5.09 (s, 2H), 4.48 (br s, 3H),4.00 (br s, 3H), 3.87 (s, 3H), 3.77 (s, 2H), 3.24-3.18 (m, 1H),2.94-2.84 (m, 1H), 1.84-1.45 (m, 4H). C₂₉H₃₂N₂O₄; MS (ESI) m/z 473.2(MH)⁺. 1081-(phenylethynyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.61-7.58 (m, 2H), 7.52-7.41 (m, 3H),7.29 (d, J = 1.8 Hz, 1H), 7.24 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 6.84(d, J = 8.2 Hz, 1H), 4.58 (s, 2H), 4.52 (br s, 1H), 4.47 (br s, 1H),4.04 (s, 2H), 3.55-3.45 (m, 1H), 3.11-3.01 (m, 1H), 2.05-1.86 (m, 4H).C₂₂H₂₂N₂O₂; MS (ESI) m/z 347.2 (MH)⁺. 111(E)-1-(3,4-difluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.71-7.63 (m,1H), 7.54 (d, J = 15.3 Hz, 1H), 7.47-7.34 (m, 1H), 7.32-7.19 (m, 4H),6.83 (d, J = 8.2 Hz, 1H), 4.58 (br s, 3H), 4.30 (br d, J = 14.3 Hz, 1H),4.03 (s, 2H), 3.43-3.35 (m, 1H), 3.06-2.97 (m, 1H), 1.98-1.81 (m, 4H).C₂₂H₂₂F₂N₂O₂; MS (ESI) m/z 385.2 (MH)⁺. 112(E)-1-(phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.30 (d, J = 1.8 Hz, 1H), 7.23 (dd, J =1.9 Hz, J = 8.2 Hz, 1H), 7.04 (d, J = 3.6 Hz, 1H), 6.83 (d, J = 8.2 Hz,1H), 6.62 (d, J = 3.6 Hz, 1H), 4.58 (s, 2H), 4.47 (br s, 1H), 4.43 (brs, 1H), 4.03 (s, 2H), 3.5-3.1 (br m, 2H), 2.03-1.84 (m, 4H).C₁₈H₁₉BrN₂O₃; MS (ESI) m/z 391.1/393.1 (MH)⁺. 113(E)-1-(naphthalene-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 8.05 (s, 1H), 7.92-7.77 (m,5H), 7.54-7.50 (m, 2H), 7.37-7.22 (m, 3H), 6.86-6.82 (m, 1H), 4.65-4.61(m, 1H), 4.60 (s, 2H), 4.37 (br d, J = 13.6 Hz, 1H), 4.03 (s, 2H), 3.44(br t, J = 12.5 Hz, 1H), 3.04 (br t, J = 12.4 Hz, 1H), 2.03-1.87 (m,4H). C₂₆H₂₆N₂O₂; MS (ESI) m/z 399.3 (MH)⁺. 1141-(5-phenyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.69-7.65 (m, 2H), 7.46-7.32 (m,6H), 7.23 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 6.83 (d, J = 8.2 Hz, 1H),4.59 (s, 2H), 4.48 (br s, 1H), 4.44 (br s, 1H), 4.04 (s, 2H), 3.5-3.2(br m, 2H), 2.05-1.84 (m, 4H). C₂₄H₂₄N₂O₂S; MS (ESI) m/z 405.1 (MH)⁺.1151-(3-phenoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.39-6.91 (m, 11H), 6.72 (d, J = 8.2 Hz,1H), 4.44 (br s, 3H), 3.94 (s, 2H), 3.68 (br d, J = 12.1 Hz, 1H),3.35-2.9 (br m, 2H), 1.87-1.64 (m, 4H). C₂₆H₂₆N₂O₃; MS (ESI) m/z 415.2(MH)⁺. 116 (E)-1-(3,4-dichloro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.87 (d, J =1.1 Hz, 1H), 7.60-7.50 (m, 3H), 7.31-7.22 (m, 3H), 6.83 (d, J = 8.1 Hz,1H), 4.58 (br s, 3H), 4.30 (br d, J = 12.8 Hz, 1H), 4.03 (s, 2H), 3.40(br t, J = 11.4 Hz, 1H), 3.02 (br t, J = 14.2 Hz, 1H), 1.98-1.85 (m,4H). C₂₂H₂₂Cl₂N₂O₂; MS (ESI) m/z 417.1/419.1 (MH)⁺. 117(E)-1-(4-phenyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.74-7.64 (m, 7H), 7.47-7.22(m, 6H), 6.83 (d, J = 8.2 Hz, 1H), 4.59 (br s, 3H), 4.34 (br d, J = 14.2Hz, 1H), 4.03 (s, 2H), 3.42 (br t, J = 10.7 Hz, 1H), 3.03 (br t, J =11.8 Hz, 1H), 1.95-1.86 (m, 4H). C₂₈H₂₈N₂O₂; MS (ESI) m/z 425.2 (MH)⁺.1181-(2,4-dimethyl-thiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.31 (d, J = 1.8 Hz, 1H), 7.23(dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H), 4.56 (br s,3H), 4.04 (br s, 3H), 3.32-3.22 (br m, 2H), 2.69 (s, 3H), 2.40 (s, 3H),1.96-1.80 (m, 4H). C₁₉H₂₃N₃O₂S; MS (ESI) m/z 358.2 (MH)⁺. 1191-(6-methyl-imidazo[1,2-a]pyridin-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 8.73 (s, 1H),8.26 (s, 1H), 7.64 (d, J = 9.6 Hz, 1H), 7.50 (dd, J = 2.0 Hz, J = 9.7Hz, 1H), 7.31 (d, J = 1.8 Hz, 1H), 7.24 (dd, J = 1.9 Hz, J = 8.2 Hz,1H), 6.83 (d, J = 8.2 Hz, 1H), 4.65-4.60 (m, 2H), 4.59 (s, 2H), 4.04 (s,2H), 3.54-3.37 (br m, 1H), 3.23-3.07 (br m, 1H), 2.08-1.84 (m, 4H).C₂₁H₂₁ClN₄O₂; MS (ESI) m/z 397.2 (MH)⁺. 1201-(5-pyridin-2-yl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 8.54-8.52 (m, 1H), 7.93-7.85 (m,2H), 7.70 (d, J = 3.8 Hz, 1H), 7.44 (d, J = 3.9 Hz, 1H), 7.37-7.33 (m,2H), 7.24 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 6.83 (d, J = 8.2 Hz, 1H),4.59 (s, 2H), 4.43 (br d, J = 12.2 Hz, 2H), 4.05 (s, 2H), 3.45-3.20 (brm, 2H), 2.05-1.84 (m, 4H). C₂₃H₂₃N₃O₂S; MS (ESI) m/z 406.2 (MH)⁺. 1211-(2-pyridin-3-yl-thiazol-4-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 9.11 (d, J = 1.6 Hz, 1H), 8.59(d, J = 4.9 Hz, 1H), 8.40-8.36 (m, 1H), 8.08 (s, 1H), 7.57-7.53 (m, 1H),7.24 (d, J = 1.8 Hz, 1H), 7.14 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 6.74(d, J = 8.2 Hz, 1H), 4.56-4.50 (m, 1H), 4.51 (s, 2H), 4.36 (br d, J =15.4 Hz, 1H), 3.95 (s, 2H), 3.34 (br t, J = 13.2 Hz, 1H), 3.06 (br t, J= 13.3 Hz, 1H), 1.99-1.74 (m, 4H). C₂₂H₂₂N₄O₂S; MS (ESI) m/z 407.3(MH)⁺. 1221-(2-pyridin-4-yl-thiazol-4-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 8.80 (d, J = 4.8 Hz, 2H), 8.35(s, 1H), 8.25 (d, J = 6.4 Hz, 2H), 7.34 (d, J = 1.8 Hz, 1H), 7.24 (dd, J= 1.8 Hz, J = 8.2 Hz, 1H), 6.84 (d, J = 8.2 Hz, 1H), 4.65-4.61 (m, 1H),4.60 (s, 2H), 4.44 (br d, J = 14.0 Hz, 1H), 4.05 (s, 2H), 3.46 (br t, J= 13.0 Hz, 1H), 3.18 (br t, J = 15.1 Hz, 1H), 2.15-1.84 (m, 4H).C₂₂H₂₂N₄O₂S; MS (ESI) m/z 407.1 (MH)⁺. 1231-(2-phenyl-4-methyl-thiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.96 (m, 2H),7.52-7.47 (m, 3H), 7.33 (d, J = 1.8 Hz, 1H), 7.24 (dd, J = 1.8 Hz, J =8.2 Hz, 1H), 6.83 (d, J = 8.2 Hz, 1H), 4.58 (s, 2H), 4.45-4.04 (br m,2H), 4.05 (s, 2H), 3.40-3.20 (br m, 2H), 2.50 (s, 3H), 2.03-1.83 (m,4H). C₂₄H₂₅N₃O₂S; MS (ESI) m/z 420.1 (MH)⁺. 1241-(2-pyridin-3-yl-4-methyl-thiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 9.13 (s, 1H),8.65 (d, J = 4.3 Hz, 1H), 8.51-8.48 (m, 1H), 7.67 (dd, J = 5.1 Hz, J =8.1 Hz, 1H), 7.25 (d, J = 1.8 Hz, 1H), 7.16 (dd, J = 1.9 Hz, J = 8.2 Hz,1H), 6.74 (d, J = 8.2 Hz, 1H), 4.49 (s, 2H), 4.40-4.00 (br m, 2H), 3.97(s, 2H), 3.35-3.15 (br m, 2H), 2.45 (s, 3H), 1.92-1.75 (m, 4H).C₂₃H₂₄N₄O₂S; MS (ESI) m/z 421.2 (MH)⁺. 1251-[2-(4-methyl-phenyl)-4-methyl-thiazol-5-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.82 (d, J =8.2 Hz, 2H), 7.32-7.30 (m, 3H), 7.23 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H),6.83 (d, J = 8.2 Hz, 1H), 4.59 (s, 2H), 4.50-4.04 (br m, 2H), 4.05 (s,2H), 3.40-3.20 (br m, 2H), 2.49 (s, 3H), 2.40 (s, 3H), 2.00-1.83 (m,4H). C₂₅H₂₇N₃O₂S; MS (ESI) m/z 434.2 (MH)⁺. 1261-(6-bromo-naphthalen-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 8.16 (s, 1H), 7.99 (s, 1H),7.95 (d, J = 8.5 Hz, 1H), 7.89 (d, J = 8.8 Hz, 1H), 7.68 (dd, J = 1.9Hz, J = 8.8 Hz, 1H), 7.59 (dd, J = 1.5 Hz, J = 8.5 Hz, 1H), 7.35 (d, J =1.8 Hz, 1H), 7.23 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 6.82 (d, J = 8.2 Hz,1H), 4.58 (br s, 3H), 4.05 (s, 2H), 3.90-3.75 (br m, 1H), 3.50-3.10 (m,2H), 2.03-1.76 (m, 4H). C₂₄H₂₃BrN₂O₂; MS (ESI) m/z 451.0/453.1 (MH)⁺.1271-[5-(1-methyl-3-trifluoromethyl-pyrazol-5-yl)-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ7.33 (d, J = 3.8 Hz, 1H), 7.29 (d, J = 3.8 Hz, 1H), 7.22 (d, J = 1.8 Hz,1H), 7.14 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 7.03 (s, 1H), 6.74 (d, J =8.2 Hz, 1H), 4.49 (s, 2H), 4.34 (br d, J = 15.3 Hz, 2H), 3.93 (s, 2H),3.92 (s, 3H), 3.35-3.15 (m, 2H), 1.95-1.74 (m, 4H). C₂₃H₂₃F₃N₄O₂S; MS(ESI) m/z 477.1 (MH)⁺. 1281-[2-(4-trifluoromethyl-phenyl)-4-methyl-thiazol-5-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ8.15 (d, J = 8.3 Hz, 2H), 7.80 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 1.9 Hz,1H), 7.24 (dd, J = 1.7 Hz, J = 8.1 Hz, 1H), 6.83 (d, J = 8.2 Hz, 1H),4.58 (s, 2H), 4.41-4.11 (br, 1H), 4.05 (br s, 3H), 3.41-3.21 (br m, 2H),2.52 (s, 3H), 2.00-1.83 (m, 4H). C₂₅H₂₄F₃N₃O₂S; MS (ESI) m/z 488.1(MH)⁺. 1291-[5-(2-chloro-5-trifluoromethyl-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ8.11 (s, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.55 (d, J = 8.4 Hz, 1H),7.28-7.09 (m, 4H), 6.74 (d, J = 8.2 Hz, 1H), 4.51 (s, 2H), 4.45 (br d, J= 14.2 Hz, 2H), 3.94 (s, 2H), 3.60-2.90 (br m, 2H), 1.98-1.77 (m, 4H).C₂₅H₂₂ClF₃N₂O₃; MS (ESI) m/z 491.1 (MH)⁺. 1301-(5-phenyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.69-7.66 (m, 2H), 7.36-7.21 (m,4H), 7.14 (dd, J = 2.0 Hz, J = 8.2 Hz, 1H), 7.06 (d, J = 3.6 Hz, 1H),6.85 (d, J = 3.6 Hz, 1H), 6.74 (d, J = 8.2 Hz, 1H), 4.52 (s, 2H),4.51-4.48 (br m, 2H), 3.94 (s, 2H), 3.50-3.10 (br m, 2H), 2.00-1.79 (m,4H). C₂₄H₂₄N₂O₃; MS (ESI) m/z 389.2 (MH)⁺. 1311-[5-(4-methyl-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.56 (d, J =8.0 Hz, 2H), 7.21 (s, 1H), 7.17-7.13 (m, 3H), 7.05 (d, J = 3.5 Hz, 1H),6.78-6.73 (m, 2H), 4.52 (s, 2H), 4.51-4.48 (br m, 2H), 3.94 (s, 2H),3.59-3.09 (br m, 2H), 2.27 (s, 3H), 1.94-1.79 (m, 4H). C₂₅H₂₆N₂O₃; MS(ESI) m/z 403.2 (MH)⁺. 1321-[5-(4-methoxy-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.63-7.58 (m,2H), 7.22 (d, J = 1.8 Hz, 1H), 7.14 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H),7.04 (d, J = 3.5 Hz, 1H), 6.92-6.87 (m, 2H), 6.74 (d, J = 8.2 Hz, 1H),6.70 (d, J = 3.5 Hz, 1H), 4.52 (s, 2H), 4.51-4.48 (br m, 2H), 3.94 (s,2H), 3.73 (s, 3H), 3.35-3.10 (br m, 2H), 1.99-1.78 (m, 4H). C₂₅H₂₆N₂O₄;MS (ESI) m/z 419.2 (MH)⁺. 1331-(3,5-di-tert-butyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.49 (d, J = 1.7 Hz, 1H), 7.24 (d,J = 1.8 Hz, 1H), 7.20 (d, J = 1.8 Hz, 2H), 7.14 (d, J = 8.2 Hz, 1H),6.73 (d, J = 8.2 Hz, 1H), 4.47 (br s, 3H), 3.95 (s, 2H), 3.71-3.67 (brm, 1H), 3.21-3.04 (br m, 2H), 1.93-1.67 (m, 4H), 1.25 (s, 18H).C₂₈H₃₈N₂O₂; MS (ESI) m/z 435.3 (MH)⁺. 1341-[5-(3-chloro-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.18-7.12 (m,3H), 6.96-6.93 (m, 2H), 6.88-6.83 (m, 2H), 6.73 (d, J = 8.1 Hz, 1H),6.57 (d, J = 3.4 Hz, 1H), 5.03 (s, 2H), 4.48 (s, 2H), 4.40-4.25 (m, 2H),3.93 (s, 2H), 3.30-3.00 (br m, 2H), 1.91-1.71 (m, 4H). C₂₅H₂₅ClN₂O₄; MS(ESI) m/z 453.1 (MH)⁺. 1351-[5-(3-trifluoromethyl-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.98-7.93 (m,2H), 7.56 (dd, J = 1.1 Hz, J = 3.6 Hz, 2H), 7.22 (d, J = 1.8 Hz, 1H),7.14 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 7.07 (d, J = 3.7 Hz, 1H), 7.03(d, J = 3.7 Hz, 1H), 6.75 (d, J = 8.2 Hz, 1H), 4.52 (s, 2H), 4.47 (d, J= 13.9 Hz, 2H), 3.94 (s, 2H), 3.50-3.00 (br m, 2H), 1.99-1.79 (m, 4H).C₂₅H₂₃F₃N₂O₃; MS (ESI) m/z 457.2 (MH)⁺. 1361-[5-(2,4-dichloro-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.78 (d, J =8.6 Hz, 1H), 7.52 (d, J = 2.1 Hz, 1H), 7.36 (dd, J = 2.2 Hz, J = 8.6 Hz,1H), 7.21 (d, J = 1.8 Hz, 1H), 7.14 (dd, J = 3.8 Hz, J = 7.5 Hz, 2H),7.09 (d, J = 3.7 Hz, 1H), 6.74 (d, J = 8.2 Hz, 1H), 4.51 (s, 2H), 4.47(d, J = 14.0 Hz, 2H), 3.94 (s, 2H), 3.50-3.00 (br m, 2H), 1.98-1.78 (m,4H). C₂₄H₂₂Cl₂N₂O₃; MS (ESI) m/z 457.2 (MH)⁺. 1371-[5-(2,5-dichloro-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.83 (d, J =2.5 Hz, 1H), 7.44 (d, J = 8.6 Hz, 1H), 7.28 (dd, J = 2.5 Hz, J = 8.6 Hz,1H), 7.21 (d, J = 3.4 Hz, 2H), 7.14 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H),7.09 (d, J = 3.7 Hz, 1H), 6.74 (d, J = 8.2 Hz, 1H), 4.52 (s, 2H), 4.47(d, J = 14.1 Hz, 2H), 3.94 (s, 2H), 3.50-3.00 (br m, 2H), 1.98-1.78 (m,4H). C₂₄H₂₂Cl₂N₂O₃; MS (ESI) m/z 457.2 (MH)⁺. 1381-[5-(3,4-dichloro-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.86 (d, J =2.0 Hz, 1H), 7.61 (dd, J = 2.1 Hz, J = 8.5 Hz, 1H), 7.50 (d, J = 8.4 Hz,1H), 7.21 (d, J = 1.8 Hz, 1H), 7.14 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H),7.06 (d, J = 3.6 Hz, 1H), 6.97 (d, J = 3.6 Hz, 1H), 6.74 (d, J = 8.2 Hz,1H), 4.52 (s, 2H), 4.46 (d, J = 14.2 Hz, 2H), 3.94 (s, 2H), 3.50-3.00(br m, 2H), 1.98-1.78 (m, 4H). C₂₄H₂₂Cl₂N₂O₃; MS (ESI) m/z 457.2 (MH)⁺.139 1-[5-(3-methyl-4-chloro-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ7.18-7.11 (m, 3H), 6.93 (d, J = 3.4 Hz, 1H), 6.84 (d, J = 2.9 Hz, 1H),6.74 (d, J = 3.0 Hz, 1H), 6.71 (d, J = 3.5 Hz, 1H), 6.55 (d, J = 3.4 Hz,1H), 4.99 (s, 2H), 4.48 (s, 2H), 4.45-4.25 (br m, 2H), 3.93 (s, 2H),3.40-2.90 (br m, 2H), 2.21 (s, 3H), 1.91-1.71 (m, 4H). C₂₆H₂₇ClN₂O₄; MS(ESI) m/z 467.3 (MH)⁺. 1401-[5-(4-bromo-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.62-7.48 (m,4H), 7.22 (d, J = 1.8 Hz, 1H), 7.14 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H),7.06 (d, J = 3.6 Hz, 1H), 6.90 (d, J = 3.56 Hz, 1H), 6.74 (d, J = 8.2Hz, 1H), 4.52 (s, 2H), 4.47 (d, J = 14.3 Hz, 2H), 3.94 (s, 2H),3.50-3.10 (br m, 2H), 1.98-1.78 (m, 4H). C₂₄H₂₃BrN₂O₃; MS (ESI) m/z467.1 (MH)⁺. 1411-(trans-2-phenyl-cyclopropyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.17-7.05 (m, 7H), 6.72 (d, J= 8.5 Hz, 1H), 4.45 (s, 2H), 4.44-4.37 (m, 1H), 4.14 (d, J = 13.1 Hz,1H), 3.92 (s, 2H), 3.28-3.25 (m, 1H), 2.84 (t, J = 13.8 Hz, 1H),2.34-2.24 (m, 1H), 2.20-2.10 (m, 1H), 1.87-1.73 (m, 4H), 1.50-1.44 (m,1H), 1.28-1.18 (m, 1H). C₂₃H₂₆N₂O₂; MS (ESI) m/z 363.3 (MH)⁺. 1421-(5-phenyl-pyridin-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 8.86 (s, 1H), 8.57 (s, 1H), 8.12(t, J = 2.0 Hz, 1H), 7.65-7.62 (m, 2H), 7.48-7.35 (m, 3H), 7.25 (d, J =1.8 Hz, 1H), 7.14 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 6.74 (d, J = 8.2 Hz,1H), 4.56-4.53 (m, 1H), 4.52 (s, 2H), 3.95 (s, 2H), 3.80-3.60 (m, 1H),3.45-3.30 (m, 1H), 3.18-3.02 (m, 1H), 1.90-1.71 (m, 4H). C₂₅H₂₅N₃O₂; MS(ESI) m/z 400.2 (MH)⁺. 1431-(5-thien-2-yl-pyridin-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 8.86 (s, 1H), 8.46 (s, 1H), 8.06(d, J = 2.0 Hz, 1H), 7.53 (d, J = 3.6 Hz, 1H), 7.48 (d, J = 5.0 Hz, 1H),7.24 (s, 1H), 7.16-7.09 (m, 2H), 6.73 (d, J = 8.2 Hz, 1H), 4.52-4.49 (m,1H), 4.48 (s, 2H), 3.95 (s, 2H), 3.80-3.60 (m, 1H), 3.45-3.30 (m, 1H),3.18-3.02 (m, 1H), 1.93-1.70 (m, 4H). C₂₃H₂₃N₃O₂S; MS (ESI) m/z 406.2(MH)⁺. 144 1-[5-(3-methoxy-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.26-7.22 (m,4H), 7.14 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 7.05 (d, J = 3.6 Hz, 1H),6.86-6.81 (m, 2H), 6.74 (d, J = 8.2 Hz, 1H), 4.52 (s, 2H), 4.51-4.46 (m,2H), 3.94 (s, 2H), 3.74 (s, 3H), 3.40-3.10 (br m, 2H), 1.99-1.79 (m,4H). C₂₅H₂₆N₂O₄; MS (ESI) m/z 419.2 (MH)⁺. 1451-[5-(4-chloro-pyrazol-1-ylmethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (DMSO_(d6)) δ 8.87 (s,1H), 8.86 (br s, 2H), 8.39 (s, 1H), 8.20 (d, J = 1.5 Hz, 1H), 8.04 (dd,J = 1.7 Hz, J = 8.2 Hz, 1H), 7.77 (d, J = 3.4 Hz, 1H), 7.66 (d, J = 8.2Hz, 1H), 7.41 (d, J = 3.4 Hz, 1H), 6.22 (s, 2H), 5.33 (s, 2H), 5.01 (brd, J = 13.7 Hz, 2H), 4.78-4.73 (m, 2H), 4.20-3.90 (br m, 2H), 2.65-2.50(m, 4H). C₂₂H₂₃ClN₄O₃; MS (ESI) m/z 427.2 (MH)⁺. 1461-[5-(2-chloro-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.53 (d, J =1.9 Hz, 1H), 7.50 (d, J = 1.9 Hz, 1H), 7.43-7.23 (m, 2H), 7.21 (d, J =1.8 Hz, 1H), 7.14 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 7.02 (d, J = 3.6 Hz,1H), 6.83 (d, J = 3.5 Hz, 1H), 6.73 (d, J = 8.2 Hz, 1H), 4.50 (s, 2H),4.40 (br d, J = 13.6 Hz, 2H), 3.94 (s, 2H), 3.50-3.00 (m, 2H), 1.97-1.76(m, 4H). C₂₆H₂₃ClN₂O₃; MS (ESI) m/z 447.1 (MH)⁺. 1471-[5-(benzylthiomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.20-7.12 (m,7H), 6.88-6.87 (m, 1H), 6.74-6.72 (m, 1H), 6.27-6.26 (m, 1H), 4.48 (s,2H), 4.40 (br d, J = 12.1 Hz, 2H), 3.94 (s, 2H), 3.64 (d, J = 3.1 Hz,2H), 3.57 (d, J = 2.7 Hz, 2H), 3.35-2.95 (br m, 2H), 1.92-1.72 (m, 4H).C₂₆H₂₈N₂O₃S; MS (ESI) m/z 449.2 (MH)⁺. 1481-[5-(4,6-dimethyl-pyrimidin-2-ylthiomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ7.17-7.12 (m, 2H), 6.87 (d, J = 3.4 Hz, 1H), 6.81 (s, 1H), 6.73 (d, J =8.1 Hz, 1H), 6.38 (d, J = 3.3 Hz, 1H), 4.46 (s, 2H), 4.43 (s, 2H),4.42-4.34 (br m, 2H), 3.94 (s, 2H), 3.25-2.9 (br m, 2H), 2.29 (s, 6H),1.87-1.70 (m, 4H). C₂₅H₂₈N₄O₃S; MS (ESI) m/z 465.2 (MH)⁺. 1491-[5-(3,5-dichloro-phenoxy)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.23-7.00 (m,6H), 6.74-6.71 (m, 1H), 5.86-5.84 (m, 1H), 4.47 (s, 2H), 4.34 (br d, J =12.5 Hz, 2H), 3.93 (s, 2H), 3.30-3.00 (br m, 2H), 1.90-1.71 (m, 4H).C₂₄H₂₂Cl₂N₂O₄; MS (ESI) m/z 473.1 (MH)⁺. 1501-[5-(3,5-dimethyl-4-bromo-pyrazol-1-yl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ7.17-7.12 (m, 2H), 6.89 (d, J = 3.4 Hz, 1H), 6.74 (d, J = 8.1 Hz, 1H),6.41 (d, J = 3.4 Hz, 1H), 5.23 (s, 2H), 4.46 (s, 2H), 4.40-4.10 (br m,2H), 3.94 (s, 2H), 3.25-2.90 (br m, 2H), 2.22 (s, 3H), 2.01 (s, 3H),1.86-1.68 (m, 4H). C₂₄H₂₇BrN₄O₃; MS (ESI) m/z 499.2 (MH)⁺. 1511-[5-(5-trifluoromethyl-pyridin-2-ylthiomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ8.64 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.36 (d, J = 8.3 Hz, 1H),7.15-7.12 (m, 2H), 6.87 (d, J = 3.4 Hz, 1H), 6.73 (d, J = 7.9 Hz, 1H),6.39 (s, 1H), 4.52 (s, 2H), 4.45 (s, 2H), 4.35 (br d, J = 12.6 Hz, 2H),3.93 (s, 2H), 3.25-2.80 (br m, 2H), 1.86-1.70 (m, 4H). C₂₅H₂₄F₃N₃O₃S; MS(ESI) m/z 504.1 (MH)⁺. 1521-[4-phenylethynyl-pyridin-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₇H₂₅N₃O₂; MS (ESI) m/z 424.2 (MH)⁺. 1531-[5-(2-methyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₇H₂₆N₂O₃; MS (ESI) m/z 427.2(MH)⁺. 1541-[5-(4-fluoro-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₅H₂₅FN₂O₄; MS (ESI) m/z437.3 (MH)⁺. 1551-(3-methylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₆N₂O₃S₂; MS(ESI) m/z 443.2 (MH)⁺. 1561-[5-(2,5-dimethyl-furan-3-yl-carbonylaminomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₆H₂₉N₃O₅; MS(ESI) m/z 464.4 (MH)⁺. 1571-(3-chloro-4-isopropylsulfonyl-5-methylthio-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₇ClN₂O₄S₃; MS(ESI) m/z 515.1 (MH)⁺. 1591-thien-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₁₈H₂₀N₂O₂S; MS (ESI) m/z 329.1 (MH)⁺. 161(E)-1-(3-fluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₃FN₂O₂; MS (ESI) m/z 367.2 (MH)⁺. 162(Z)-1-(1-fluoro-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₃FN₂O₂; MS (ESI) m/z 367.2 (MH)⁺. 1631-(5,6,7-trihydro-4H-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₆N₂O₂S; MS (ESI) m/z383.3 (MH)⁺. 164(E)-1-(3-chloro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan],; MS (ESI) m/z 467.1 (MH)⁺. C₂₂H₂₃ClN₂O₂; MS(ESI) m/z 383.1 (MH)⁺. 165(E)-1-(4-chloro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], C₂₂H₂₃ClN₂O₂; MS (ESI) m/z 383.1 (MH)⁺. 1661-(3-chloro-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₁ClN₂O₂S; MS (ESI) m/z 413.1 (MH)⁺. 167(E)-1-(3-trifluoromethoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₃F₃N₂O₃; MS (ESI) m/z433.2 (MH)⁺. 1681-(4-fluoro-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₁FN₂O₂S; MS (ESI) m/z 397.2 (MH)⁺. 1691-(5-methylsulfonyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₁₉H₂₂N₂O₄S₂; MS (ESI) m/z 407.1 (MH)⁺. 1701-[5-(4-methyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₇H₂₆N₂O₃; MS (ESI) m/z 427.2(MH)⁺. 1711-(3-chloro-6-fluoro-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₀ClFN₂O₂S; MS (ESI) m/z431.1 (MH)⁺. 1721-[5-(2,5-dimethyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₈H₂₈N₂O₃; MS (ESI) m/z 441.3(MH)⁺. 1731-[5-(2-methoxy-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₇H₂₆N₂O₄; MS (ESI) m/z 443.2(MH)⁺. 1741-[5-(2,5-dimethyl-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₇H₃₀N₂O₄; MS (ESI) m/z 447.3(MH)⁺. 175 1-(3,4-dichloro-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₀Cl₂N₂O₂S; MS (ESI) m/z447.1 (MH)⁺. 1761-[5-(3,5-difluoro-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₆H₂₂F₂N₂O₃; MS (ESI) m/z449.2 (MH)⁺. 1771-(5-naphthalen-1-ylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₃₀H₂₆N₂O₃; MS (ESI) m/z 463.2(MH)⁺. 1781-[5-(4-tert-butyl-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₉H₃₄N₂O₄; MS (ESI) m/z 475.4(MH)⁺. 179(E)-1-(3-methyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₆N₂O₂; MS (ESI) m/z 363.3 (MH)⁺. 180(E)-1-(4-methyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₆N₂O₂; MS (ESI) m/z 363.3 (MH)⁺. 181(Z)-1-(1-methyl-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₆N₂O₂; MS (ESI) m/z 363.3(MH)⁺. 182(E)-1-(4-fluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₃FN₂O₂; MS (ESI) m/z 367.2 (MH)⁺. 183(Z)-1-(2-methoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₆N₂O₃; MS (ESI) m/z 379.2(MH)⁺. 184 (E)-1-(3-methoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₆N₂O₃; MS (ESI) m/z 379.2(MH)⁺. 185 (E)-1-(4-methoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₆N₂O₃; MS (ESI) m/z 379.2(MH)⁺. 186(E)-1-(2-chloro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₃ClN₂O₂; MS (ESI) m/z 383.2 (MH)⁺. 187(E)-1-(benzodioxol-5-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₄N₂O₄; MS (ESI) m/z 392.9 (MH)⁺. 187(E)-1-(benzodioxol-5-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₄N₂O₄; MS (ESI) m/z 392.9 (MH)⁺. 188(E)-1-(naphthalen-1-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₆H₂₆N₂O₂; MS (ESI) m/z 399.1 (MH)⁺. 1891-(1-oxo-2-fluoren-9-ylidene-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₈H₂₆N₂O₂; MS (ESI) m/z 423.3 (MH)⁺. 190(E)-1-(1-phenyl-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₈H₂₈N₂O₂; MS (ESI) m/z 425.2(MH)⁺. 191(E)-1-(2-methyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₆N₂O₂; MS (ESI) m/z 363.3 (MH)⁺. 1921-(1-methyl-3H-inden-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₄H₂₆N₂O₂; MS (ESI) m/z 375.3 (MH)⁺. 1931-(1-methyl-indol-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₅N₃O₂; MS (ESI) m/z 376.2 (MH)⁺. 194(E)-1-(2-methoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₆N₂O₃; MS (ESI) m/z 379.2(MH)⁺. 195 (E)-1-(2,6-difluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₂F₂N₂O₂; MS (ESI) m/z385.2 (MH)⁺. 1961-(2-oxo-(2H)-chromen-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₂N₂O₄; MS (ESI) m/z 391.2 (MH)⁺. 1971-(8-methoxy-(2H)-chromen-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₄H₂₆N₂O₄; MS (ESI) m/z 407.3(MH)⁺. 1981-(5-bromo-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₁₈H₁₉BrN₂O₂S; MS (ESI) m/z 407.0 (MH)⁺. 199(E)-1-(2-bromo-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₃BrN₂O₂; MS (ESI) m/z 427.1 (MH)⁺. 2001-(5-trifluoromethyl-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₁F₃N₂O₂S; MS (ESI) m/z447.1 (MH)⁺. 2011-[3-(4-methoxy-phenyl)-4-cyano-5-methylthio-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₇H₂₇N₃O₃S₂; MS(ESI) m/z 506.1 (MH)⁺. 2021-[3-(4-chloro-phenyl)-4-cyano-5-methylthio-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₆H₂₄ClN₃O₂S₂; MS(ESI) m/z 510.1 (MH)⁺. 2031-(5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₆N₂O₂S; MS (ESI) m/z383.0 (MH)⁺. 2041-thieno[3,2-b]thien-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₀H₂₀N₂O₂S₂; MS (ESI) m/z 384.9 (MH)⁺. 205(Z)-1-(1-methylcarbonylamino-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₄H₂₇N₃O₃; MS (ESI) m/z 405.9(MH)⁺. 2061-[5-(2-methyl-thiazol-4-yl)-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₃N₃O₂S₂; MS (ESI) m/z425.9 (MH)⁺. 2071-(3-chloro-6-methyl-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₃ClN₂O₂S; MS (ESI) m/z426.9 (MH)⁺. 2071-(3-chloro-6-methyl-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₃ClN₂O₂S; MS (ESI) m/z428.9 (MH)⁺. 208 1-[3-(2-methyl-phenoxy)-benzyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₈H₃₀N₂O₃; MS (ESI) m/z 443.0(MH)⁺. 2091-(3-chloro-6-methoxy-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₃ClN₂O₃S; MS (ESI) m/z442.8 (MH)⁺. 2101-[3-(2-fluoro-phenoxy)-benzyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₇H₂₇FN₂O₃; MS (ESI) m/z 446.9 (MH)⁺. 2111-(3-propylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₅H₃₀N₂O₃S₂; MS(ESI) m/z 470.9 (MH)⁺. 2121-[5-(2-methoxy-4-propyl-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₉H₃₄N₂O₅; MS(ESI) m/z 491.0 (MH)⁺. 2131-[5-(2-bromo-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₅H₂₅BrN₂O₄; MS (ESI) m/z496.8 (MH)⁺. 2141-(3-benzylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₉H₃₀N₂O₃S₂; MS(ESI) m/z 518.8 (MH)⁺. 2151-[1-oxo-2-(3-oxo-3H-isobenzofuran-1-ylidene)-ethyl]-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₂N₂O₄; MS (ESI) m/z 390.9(MH)⁺. 216 1-(5-morpholin-4-ylmethyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₉N₃O₄; MS (ESI) m/z 411.9(MH)⁺. 217 1-(4-phenyl-[1,2,3]thiadiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₂N₄O₂S; MS (ESI) m/z407.0 (MH)⁺. 2181-(3-methylthio-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ7.23 (d, J = 1.9 Hz, 1H), 7.25 (dd, J = 1.9 Hz, J = 8.2 Hz, 1H), 6.84(d, J = 8.2 Hz, 1H), 4.58 (s, 2H), 4.23 (br d, J = 13.6 Hz, 2H), 4.06(s, 2H), 3.25 (br t, J = 11.7 Hz, 2H), 2.76-2.67 (m, 4H), 2.43 (s, 3H),1.99-1.78 (m, 8H). C₂₃H₂₈N₂O₂S₂; MS (ESI) m/z 429.0 (MH)⁺. 2191-(3-methylthio-7-hydro-6H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₆N₂O₂S₂; MS (ESI) m/z426.9 (MH)⁺. 2201-[5-(2-methyl-furan-3-yl-carbonylaminomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₅H₂₇N₃O₅; MS(ESI) m/z 449.9 (MH)⁺. 2211-[5-(3,5-dimethyl-4-chloro-pyrazol-1-yl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₄H₂₇ClN₄O₃ MS(ESI) m/z 455.0 (MH)⁺. 2221-(3-methyl-4-oxo-6-phenyl-5,6,7-trihydro-4H-benzo[b]furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan]C₂₉H₃₀N₂O₄; MS (ESI) m/z 470.9 (MH)⁺. 2231-(3-ethylthio-4-oxo-6,6-dimethyl-6,7-dihydro-5H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan]C₂₆H₃₂N₂O₃S₂; MS (ESI) m/z 485.0 (MH)⁺. 2241-[5-(2-methoxy-4-allyl-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₉H₃₂N₂O₅; MS(ESI) m/z 489.0 (MH)⁺. 2251-(3-isopropylthio-4-oxo-6,6-dimethyl-6,7-dihydro-5H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan]C₂₇H₃₄N₂O₃S₂; MS (ESI) m/z 498.9 (MH)⁺. 2261-(3,4-dimethyl-5-cyano-thieno[2,3-b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₃N₃O₂S₂; MS (ESI) m/z437.9 (MH)⁺. 2271-[5-(3-methoxy-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₆H₂₈N₂O₅; MS (ESI) m/z 449.0(MH)⁺. 2281-(3-methyl-6-phenyl-benzo[b]furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₉H₂₈N₂O₃; MS (ESI) m/z 452.9(MH)⁺. 2291-(3-butylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₆H₃₂N₂O₃S₂; MS(ESI) m/z 484.8 (MH)⁺. 2301-(3-chloro-6-bromo-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₀BrClN₂O₂S; MS (ESI) m/z491.0 (MH)⁺. 2311-(3-sec-butylthio-4-oxo-6,6-dimethyl-6,7-dihydro-5H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan]C₂₈H₃₆N₂O₃S₂; MS (ESI) m/z 512.8 (MH)⁺. 2321-(3-benzylthio-4-oxo-6,6-dimethyl-6,7-dihydro-5H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan]C₃₁H₃₄N₂O₃S₂; MS (ESI) m/z 546.9 (MH)⁺. 2331-thieno[2,3-b]thien-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₀H₂₀N₂O₂S₂; MS (ESI) m/z 384.9 (MH)⁺. 2341-(3-methylthio-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₄N₂O₂S₂; MS (ESI) m/z424.8 (MH)⁺. 2351-(3-Methylthio-4-methoxy-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₄H₂₆N₂O₃S₂; MS (ESI) m/z454.8 (MH)⁺. 2361-indol-3-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₃N₃O₂; MS (ESI) m/z 362.0 (MH)⁺. 2371-(1-methyl-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₅N₃O₂; MS (ESI) m/z 375.9 (MH)⁺. 2381-(5-methoxy-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₅N₃O₃; MS (ESI) m/z 392.0 (MH)⁺. 2391-(1-benzyl-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₉H₂₉N₃O₂; MS (ESI) m/z 452.0 (MH)⁺. 2401-(3-benzylthio-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₉H₂₈N₂O₂S₂; MS (ESI) m/z500.9 (MH)⁺. 2411-(3-benzylthio-7-hydro-6H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₉H₃₀N₂O₂S₂; MS (ESI) m/z502.8 (MH)⁺. 242(Z)-1-(furan-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₀H₂₂N₂O₃; MS (ESI) m/z 338.9 (MH)⁺. 243(Z)-1-(imidazol-4-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₁₉H₂₂N₄O₂; MS (ESI) m/z 339.0 (MH)⁺. 244(E)-1-(pyridin-4-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₁H₂₃N₃O₂; MS (ESI) m/z 350.0 (MH)⁺. 2451-(5-formyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₁₉H₂₀N₂O₃S; MS (ESI) m/z 356.9 (MH)⁺. 2461-(5,6-dihydro-4H-cyclopenta[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₁H₂₄N₂O₂S; MS (ESI) m/z368.9 (MH)⁺. 2471-(5-methylthio-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₁₉H₂₂N₂O₂S₂; MS (ESI) m/z 374.9 (MH)⁺. 248(E)-1-(1-cyano-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₃N₃O₂; MS (ESI) m/z 374.0(MH)⁺. 2491-(7-methyl-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₅N₃O₂; MS (ESI) m/z 375.9 (MH)⁺. 2501-(1-ethyl-7-methyl-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₅H₂₉N₃O₂; MS (ESI) m/z 404.0 (MH)⁺. 251(E)-1-(furan-3-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₀H₂₂N₂O₃; MS (ESI) m/z 339.0 (MH)⁺. 252(E)-1-(pyridin-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₁H₂₃N₃O₂; MS (ESI) m/z 350.0 (MH)⁺. 253(E)-1-(pyridin-3-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₁H₂₃N₃O₂; MS (ESI) m/z 350.0 (MH)⁺. 254(E)-1-(thien-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₀H₂₂N₂O₂S; MS (ESI) m/z 354.9 (MH)⁺. 255(E)-1-(thien-3-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₀H₂₂N₂O₂S; MS (ESI) m/z 354.9 (MH)⁺. 2561-(5-dihydroxymethyl-4-methyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] ¹H NMR (CD₃OD) δ 7.32 (d, J =1.7 Hz, 1H), 7.23 (dd, J = 1.8 Hz, J = 8.2 Hz, 1H), 7.17 (s, 1H), 6.82(d, J = 8.2 Hz, 1H), 5.66 (s, 1H), 4.57 (s, 2H), 4.39 (br d, J = 11.7Hz, 2H), 4.04 (s, 2H), 3.35-3.15 (br m, 2H), 2.24 (s, 3H), 2.03-1.81 (m,4H). C₂₀H₂₄N₂O₄S 2571-(5,6,7,8-tetrahydro-4H-cyclohepta[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₈N₂O₂S; MS(ESI) m/z 396.9 (MH)⁺. 2581-(4-cyano-5-methylthio-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₀H₂₁N₃O₂S₂; MS (ESI) m/z399.9 (MH)⁺. 2591-(4-methyl-5-bromo-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₁₉H₂₁BrN₂O₂S; MS (ESI) m/z 420.8 (MH)⁺. 260spiro[cyclohexane-1,6′-5,7-dihydro-4H-benzo[b]thiophene]-2′-carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₇H₃₄N₂O₂S; MS(ESI) m/z 450.9 (MH)⁺. 2611-(3-ethoxy-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₄H₂₈N₂O₄S; MS(ESI) m/z 440.9 (MH)⁺. 2641-(4-hydroxy-phenylethynyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₂N₂O₃; MS (ESI) m/z 362.9 (MH)⁺. 265(E)-1-(3-hydroxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₄N₂O₃; MS (ESI) m/z 365.0(MH)⁺. 2661-(5-tert-butyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₈N₂O₂S; MS (ESI) m/z 384.9 (MH)⁺. 2671-(5-methoxycarbonyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₀H₂₂N₂O₄S; MS (ESI) m/z386.9 (MH)⁺. 268(E)-1-(4-tert-butyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₆H₃₂N₂O₂; MS (ESI) m/z 405.0(MH)⁺. 2691-fluoren-1-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₇H₂₆N₂O₂; MS (ESI) m/z (MH)⁺. 2701-(9-oxo-fluoren-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₇H₂₄N₂O₃; MS (ESI) m/z 410.9 (MH)⁺. 2711-(3-chloro-6-ethyl-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₄H₂₅ClN₂O₂S; MS (ESI) m/z440.9 (MH)⁺. 272 (E)-1-(2-hydroxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₄N₂O₃; MS (ESI) m/z 365.0(MH)⁺. 2731-(3-aminocarbonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₁H₂₃N₃O₃; MS (ESI) m/z 365.9 (MH)⁺. 2741-(3-tert-butyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₄H₃₀N₂O₂; MS (ESI) m/z 378.9 (MH)⁺. 2751-(3,4,5-trichloro-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₁₈H₁₇Cl₃N₂O₂S; MS (ESI) m/z 430.6 (MH)⁺. 2761-(4-trifluoromethyl-6-methyl-1H-thieno[2,3-c]pyrazol-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₁H₂₁F₃N₄O₂S; MS(ESI) m/z 450.8 (MH)⁺. 2771-(3-thien-2-yl-[1,2,4]oxadiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₆H₂₄N₄O₃S; MS (ESI) m/z472.8 (MH)⁺. 2781-(4,5-dibromo-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₁₈H₁₈Br₂N₂O₂S; MS (ESI) m/z 486.6 (MH)⁺. 2791-[4-(3,5-bis-trifluoromethyl-phenoxy)-phenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₈H₂₄F₆N₂O₃; MS (ESI) m/z550.8 (MH)⁺. 2801-(3,4-dichlorophenyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₁₉H₂₀Cl₂N₂O₃S; MS (ESI) m/z 426.7 (MH)⁺. 281(E)-1-(3-benzyloxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₉H₃₀N₂O₃; MS (ESI) m/z 455.0(MH)⁺. 2821-[5-(4-tert-butyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₃₀H₃₂N₂O₃; MS (ESI) m/z 468.9(MH)⁺. 283 1-(1-phenylsulfonyl-1H-indol-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₈H₂₇N₃O₄S; MS (ESI) m/z501.9 (MH)⁺. 2841-[3-(3-thien-2-yl-[1,2,4]oxadiazol-5-yl)-5-aminocarbonyl-phenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan]C₂₇H₂₅N₅O₄S; MS (ESI) m/z 515.8 (MH)⁺. 2861-3H-inden-1-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₄N₂O₂; MS (ESI) m/z 360.1 (MH)⁺. 2871-(3-oxo-indan-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₃H₂₄N₂O₃; MS (ESI) m/z 377.1 (MH)⁺. 2881-(4-phenyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₄H₂₄N₂O₂S; MS (ESI) m/z 405.1 (MH)⁺. 2891-fluoren-9-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₇H₂₆N₂O₂; MS (ESI) m/z 411.1 (MH)⁺. 2901-(1-oxo-2,2-diphenyl-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₇H₂₈N₂O₂; MS (ESI) m/z 413.0 (MH)⁺. 291(E)-1-[3-(2-methoxy-ethoxy)-phenylethenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₅H₃₀N₂O₄; MS (ESI) m/z 423.2(MH)⁺. 2921-9H-xanthen-9-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₇H₂₆N₂O₃; MS (ESI) m/z 427.1 (MH)⁺. 2931-9H-xanthen-9-ylmethylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₈H₂₈N₂O₃; MS (ESI) m/z 440.9 (MH)⁺. 294(E)-1-(3-phenethoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₃₀H₃₂N₂O₃; MS (ESI) m/z 469.1(MH)⁺. 2951-(4-phenyl-5-trifluoromethyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₅H₂₃F₃N₂O₂S; MS (ESI) m/z473.0 (MH)⁺. 2981-(1-chloro-naphtho[2,1-b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₆H₂₃ClN₂O₂S; MS (ESI) m/z462.7 (MH)⁺. 2991-[3-(4-chloro-phenyl)-5-methylthio-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₅H₂₅ClN₂O₂S₂; MS (ESI) m/z484.8 (MH)⁺. 300(E)-1-(4-benzyloxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₉H₃₀N₂O₃; MS (ESI) m/z 455.0(MH)⁺. 301(E)-1-[3-(3-methoxy-propoxy)-phenylethenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₆H₃₂N₂O₄; MS (ESI) m/z 437.1(MH)⁺. 302(E)-1-[3-(2-ethoxy-ethoxy)-phenylethenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₆H₃₂N₂O₄; MS (ESI) m/z 437.1(MH)⁺. 3031-(3-methyl-4-bromo-5-propoxy-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₇BrN₂O₃S; MS (ESI) m/z479.2 (MH)⁺. 309(E)-1-(2-fluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₂H₂₃FN₂O₂; MS (ESI) m/z 367.2 (MH)⁺. 3541-(2,2-diphenylethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₈H₃₀N₂O₂; MS (ESI) m/z 426.9 (MH)⁺. 3551-(9H-fluoren-9-ylmethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₈H₂₈N₂O₂; MS (ESI) m/z 425.0 (MH)⁺. 356(E)-1-(3-methyl-thien-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₁H₂₄N₂O₂S; MS (ESI) m/z368.5 (MH)⁺. 3571-[4-(4-chloro-phenyl)-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan] C₂₄H₂₃ClN₂O₂S; MS (ESI) m/z438.7 (MH)⁺.

Example 35′-(3,4-dichlorophenylcarbonylaminomethyl)-spiro[piperidine-4,3′-(2H)-benzo[b]furan](Cpd 2)

Step A.1-(tert-butyloxy)carbonyl-5′-(3,4-dichlorophenylcarbonyl-aminomethyl)-spiro[piperidine-4,3′-benzo[b]furan]

A mixture of intermediate 1f (9 mg, 0.028 mmol; Example 1),3,4-dichlorobenzoic acid (8 mg, 0.042 mmol), EDC (8 mg, 0.042 mmol),HOBt (6 mg, 0.042 mmol), and DIPEA (0.1 mL) in CH₂Cl₂ (2 mL) was stirredat room temperature for 36 h. The reaction mixture was concentrated andthe residue was purified by chromatography on silica gel eluting withCH₂Cl₂/MeOH (200:1) to give 3a (14 mg, 100%).

Step B.5′-(3,4-dichlorophenylcarbonylaminomethyl)-spiro[piperidine-4,3′-(2H)-benzo[b]furan](Cpd 2)

Compound 3a (14 mg, 0.028 mmol) was treated with a mixture of TFA/CH₂Cl₂(1:2) containing thioanisole (0.2 mL) at room temperature for 1 h. Thereaction was concentration in vacuo and the residue was purified bychromatography on silica gel eluting with CH₂Cl₂/MeOH/concd NH₄OH(100:10:1) to give the free base of Compound 2 (12.3 mg, 88%), which wasconverted to TFA salt by treatment of with a solution of TFA in CH₂Cl₂(5%) followed by concentration in vacuo. ¹H NMR (CDCl₃, 400 MHz) 7.90(s, 1H), 7.63 (d, 1H, J=8.3 Hz), 7.51 (d, 1H, J=8.4 Hz), 7.18-7.16 (m,2H), 6.80 (d, 1H, J=8.7 Hz), 6.50 (br s, 1H), 4.56 (d, 2H, J=5.7 Hz),4.43 (s, 2H), 3.36 (br s, 2H), 3.25 (d, 2 H, J=12.2 Hz), 2.82 (t, 2H,J=12.2 Hz), 2.00 (dt, 2H, J=14.1, 3.9 Hz), 1.81 (d, 2H, J=13.1 Hz); MS(ES) m/z 390.9 (MH)⁺ for C₂₀H₂₀Cl₂N₂O₂.

Example 41-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-indane](Cpd 318)

Step A. 6-bromo-1H-indene

Sodium borohydride (1.1 g, 0.029 mol) was added, in 3 portions, to asolution of 5-bromo-indan-1-one (3.09 g, 0.0136 mol; CAS#34598-49-7) inmethanol (25 mL) at 0° C. under an atmosphere of argon. After 2 h, thereaction mixture was partitioned between EtOAc and water. The organiclayer was separated, extracted with water, brine, dried (Na₂SO₄) andconcentrated in vacuo to give an amber solid (3.16 g). This solid (1.58g) was dissolved in ethylene glycol (63 mL) and treated with 20% vol.aq. sulfuric acid (63 mL). The reaction mixture was heated to 75° C. for2 hours then cooled to room temperature and extracted with DCM (2×). Thecombined organic layers were extracted with saturated aq. NaHCO₃, dried(Na₂SO₄) and concentrated in vacuo. The resulting residue was purifiedby silica gel column eluted with hexanes to afford 4a (0.76 g, 52%) as aclear liquid.

Step B. 1-(tert-butyloxy)carbonyl-spiro[piperidine-4,3′-indane]

To a solution of bis(2-chloroethyl)amine hydrochloride (2.0 g, 11 mmol;CAS#821-48-7), TEA (1.9 mL, 13 mmol) in DCM (50 mL) was addeddi-tert-butyl dicarbonate (2.9 g, 13 mmol) and allowed to stir 16 h atroom temperature under an atmosphere of argon. The reaction mixture wasdiluted with water and the organic layer separated. The organic layerwas extracted with 1 N aq. HCl, saturated aq. NaHCO₃, dried (Na₂SO₄),and concentrated in vacuo. The resulting residue was purified on silicagel column eluted with 3:2 hexanes/EtOAc to yieldbis(2-chloroethyl)carbamic acid tert-butyl ester (1.5 g, 55%).

A solution of lithium hexamethyldisilazide in THF (7.8 mL, 1 M, 7.8mmol) was added dropwise to a solution of 4a (759 mg, 3.89 mmol) in THF(5 mL) at 0° C. under an atmosphere of argon. After stirring for 45minutes, a solution of bis(2-chloroethyl)carbamic acid tert-butyl ester(0.94 g, 3.9 mmol) in THF (5 mL) was added dropwise. After stirring for2 h at 0° C., the reaction mixture was quenched with saturated aq.NH₄Cl. The resulting mixture was extracted with EtOAc. The organic layerwas separated, dried (Na₂SO₄), and concentrated in vacuo. The resultingresidue was purified on silica gel column eluted with 4:1 hexanes/EtOActo yield 4b as a clear syrup (467 mg, 33%).

Step C.1-(tert-butyloxy)carbonyl-spiro[piperidine-4,3′-indane]-5′-carboxaldehyde

A slurry of 4b (600. mg, 1.65 mmol), tris(3-chlorophenyl)phosphine (11mg, 0.03 mmol), bis(triphenylphosphine)palladium(II) bromide (24 mg,0.03 mmol), sodium formate (166 mg, 2.44 mmol) in DMF (1.7 mL) washeated to 110° C. under an atmosphere of carbon monoxide. After 3 h, thereaction was cooled to room temperature and filtered through a nylonfilter. The filtrate was diluted with 0.5 N aq. NaOH and DCM. Theorganic layer was separated, extracted with water, dried (Na₂SO₄) andconcentrated in vacuo. The resulting residue was purified on a silicagel column eluted with 4:1 hexanes/EtOAc to give 4c as a yellow syrup(296 mg, 51%).

Step D.1-(tert-butyloxy)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-indane]

To a solution of 4c (104 mg, 0.330 mmol) in absolute ethanol (1 mL) wasadded anhydrous hydrazine (0.052 mL, 1.65 mmol) at room temperature.After stirring for 2 h, the reaction mixture was concentrated in vacuo.The residue was dissolved in methanol (5 mL) and PtO₂ (0.06 mmoL, 14 mg)added. The slurry was shaken under 50 psi H₂ at room termperature. After16 h, the reaction mixture was filter through a nylon filter,concentrated in vacuo and purified by reverse-phase HPLC eluting on aC18 column with a gradient of 1:4 to 9:1 ACN/water containing 0.1% TFAto furnish 4d as a white powder (42 mg, 29%).

Step E. 1-(tert-butyloxy)carbonyl-spiro[piperidine-4,3′-indane]

A solution of 4d (42 mg, 0.10 mmol), phthalic anhydride (15 mg, 0.1mmol) and DIPEA (0.042 mL, 0.24 mmol) in toluene (1 mL) was refluxedwith a Dean-Stark trap. After 16 hrs, the reaction mixture was cooled toRT and extracted with 10% wt. aq. citric acid, brine, dried (Na₂SO₄),concentrated in vacuo. The residue was purified on silica gel columneluting with hexanes/EtOAc (4:1) to give 4e as a colorless liquid (28mg, 63%).

Step F.1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-spiro[piperidine-4,3′-indane]

To a solution of 4e (28 mg, 0.063 mmol) in DCM (5 mL) was added TFA (1mL) at RT. After 15 minutes, the reaction mixture was concentrated invacuo and the residue was dissolved in DCM. The DCM solution wasextrated with 10% wt. aq. Na₂CO₃, dried (Na₂SO₄), and concentrated invacuo. To the resulting residue was added5-phenylethynylfuran-2-carboxylic acid (34 mg, 0.16 mmol), EDC (30 mg,0.16 mmol) and DMF (1 mL). This mixture was stirred 16 hrs at RT underan argon atmosphere. The reaction mixture was diluted with EtOAc andextracted with water (3×), saturated aq. NaHCO₃ (3×), dried (Na₂SO₄) andconcentrated in vacuo. The resulting residue was purified on silica geleluted with 1:1 EtOAc/hexanes to give 4f as a colorless film (18 mg,53%).

Step G.1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-indane](Cpd 318)

To a solution of 4f (18 mg, 0.033 mmol) in ethanol (5 mL) was addedanhydrous hydrazine (1 mL) at RT. After 3 hrs, the reaction mixture wasconcentrated in vacuo and purified by C18 reverse-phase HPLC elutingwith a gradient of 3:17 to 9:1 ACN/water containing 0.1% TFA to give theTFA salt of Compound 318 as a white powder (6.3 mg, 34%): ¹H NMR (CD₃OD)δ 7.53 (m, 2H), 7.42 (m, 3H), 7.29 (m, 3H), 7.08 (d, J=3.6 Hz, 1H), 6.85(d, J=3.5 z, 1H), 4.54 (m, 2H), 4.07 (s, 2H), 3.54 (m, 1H), 2.98 (t,J=7.4 Hz, 2H), 2.73 (m, 1H), 2.25 (t, J=7.3 Hz, 2H), 1.95 (m, 2H), 1.72(m, 2H); MS (ES) m/z 410.9 (MH)⁺.

Example 51-(3,4-dichlorophenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]thiophene](Cpd 353)

Step A.4-(2-bromo-phenylsulfanylmethyl)-3,6-dihydro-2H-pyridine-1-carboxylicacid tert-butyl ester

Finely ground K₂CO₃ (3.58 g, 25.9 mmol) was added to a solution of2-bromothiophenol (1.14 mL, 9.49 mmol) and 1c (2.00 g, 8.63 mmol; 1c,Example 1) in dry acetone (48 mL). The reaction mixture was heated atreflux for 18 h while stirring under argon. The reaction mixture wasfiltered and the filtrate was concentrated in vacuo and partitionedbetween EtOAc and 5% aqueous K₂CO₃. The organic layer was extracted 5%aqueous K₂CO₃ (2×), brine (2×), dried (MgSO₄), filtered through filteragent and concentrated in vacuo to furnish 5a (3.09 g, 93%) as a brownoil.

Step B.1-(tert-butyloxy)carbonyl-spiro[piperidine-4,3′-(2H)-benzo[b]thiophene]

A solution of 5a (3.08 g, 8.01 mmol) and Bu₃SnH (5.43 mL, 20.2 mmol) intoluene (401 mL) was treated with AIBN (0.066 g, 0.402 mmol). Thereaction mixture was heated at 80° C. under argon for 18 h, cooled toroom temperature, and concentrated in vacuo. The residue was dissolvedin EtOAc, cooled to 5° C. and treated with DBU (5.5 mL, 37.2 mmol).Bromine was added dropwise until a brown endpoint was reached. Theresulting precipitate was removed by filtration through a bed of silicagel. The filtrate was extracted with 1 N aqueous Na₂S₂O₄ (2×), brine(2×), dried (MgSO₄), filtered through filter agent and concentrated invacuo. The residue was purified by chromatography on silica gel elutingwith 0-20% EtOAc in hexane to give 5b (0.77 g, 32%) as a clear oil.

Step C. spiro[piperidine-4,3′-(2H)-benzo[b]thiophene]

A solution of 5b (0.076 g, 0.249 mmol) was dissolved in a 4:1 mixture ofDCM/TFA and stirred for 1 h at room temperature under an argonatmosphere. The reaction mixture was concentrated in vacuo and theresidue was partitioned between 1.0 N aq. NaOH and diethylether. Thebasic aqueous layer was extracted 2 more times with diethylether and thecombined diethylether extracts were washed twice with brine, dried overyanhydrous K₂CO₃, and filtered. The filtrate was concentrated in vacuo toafford 5c as a clear waxy solid (37 mg, 72%).

Step D.1-(3,4-dichlorophenyl)carbonyl-spiro[piperidine-4,3′-(2H)-benzo[b]thiophene]

A solution of 5c (0.200 g, 0.974 mmol), 3,4-dichlorobenzoic acid (0.205g, 1.07 mmol) and DIPEA (0.51 mL, 2.92 mmol) in dry dichloromethane (6mL) was treated with BOP-Cl (0.298 g, 1.17 mmol) and stirred at roomtemperature for 1 h under an argon atmosphere. The reaction mixture wasconcentrated in vacuo and the residue was partitioned between EtOAc and10% aq. citric acid. The EtOAc layer was extracted twice with 10% aq.citric acid, saturated aq. NaHCO₃, and brine, then dried over anhydrousMgSO₄ and filtered. The filtrate ws concentrated in vacuo and theresidue was purified by chromatrography on silica gel eluting withhexane/EtOAc (4:1) to furnish 5d (0.200 g, 54%) as a white sold.

Step E. 1-(3,4-dichlorophenyl)carbonyl5′-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-spiro[piperidine-4,3′-(2H)-benzo[b]thiophene]

A solution of 5d (0.144 g, 0.382 mmol) in 8 mL of a mixture of glacialacetic acid and concentrated H₂SO₄ (9:1) was warmed to 60° C. andtreated with (N-hydroxymethyl)phthalimide (0.068 g, 0.382 mmol) whilestirring under an argon atmosphere. After 16 h, the reaction mixture waspoured onto ice and extracted three times with EtOAc. The combined EtOAclayers were extracted twice with saturated aq. NaHCO₃ and brine, driedover anhydrous MgSO₄ and filitered. The filtrate was purified bychromatography on silica gel eluting with hexane/EtOAc (1:1) to give 5e(0.041 g, 20%) as white solid.

Step F.1-(3,4-dichlorophenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]thiophene](Cpd 353)

A solution of 5e (0.014 g, 0.026 mmol) in 5.5 mL of a mixture ofabsolute ethanol and methylhydrazine (10:1) was heated at 40° C. for 6 hunder nitrogen. The reaction mixture was concentrated in vacuo and theresidue was purified by reverse-phase HPLC eluting on a C18 column witha gradient of 20-80% acetonitrile in water containing 0.1% TFA to givethe TFA salt of Compound 353 (0.012 g, 81%) as a white solid: ¹H NMR(CD₃OD) δ 7.75-7.60 (m, 2H), 7.45-7.30 (m, 1H), 7.35-7.20 (m, 3H),4.80-4.50 (br m, 1H), 4.07 (s, 2H), 3.80-3.60 (m, 1H), 3.52 (s, 1H),3.51-3.10 (ov m, 2H), 2.10-175 (br m, 4H); MS (ES) m/z 407.1 (MH)⁺ forC₂₀H₂₀Cl₂N₂OS.

Example 61-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole](Cpd 319)

Step A. 1-methyl-1′-formyl-spiro[piperidine-4,3′-(2H)-indole]

A solution of 1,2-dihydro-1′-methyl-spiro[3H-indole-3,4′-piperidine](29.8 g, 0.148 mol; CAS#69584-91-4; J. Med. Chem. 1983, 26, 981-986) intoluene (737 mL) was treated with formic acid (27.8 mL, 0.737 mol). Thereaction vessel was fitted with a Dean-Stark trap and the reactionmixture, which appears as two layers, was heated at reflux undernitrogen with azeotropic removal of water for 16 h. The reaction mixturewas cooled to room temperature and concentrated invacuo. The residue waspartitioned between chloroform (500 mL) and 3N aq. NaOH (300 mL). Theorganic layer was extracted three more times with N aq. NaOH (300 mL),dried over anhydrous K₂CO₃, and filtered. The filtrate was concentratedin vacuo to furnish 6a (33.5 g, 99%) as a beige solid.

Step B.5′-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-1′-formyl-1-methyl-spiro[piperidine-4,3′-(2H)-indole]

Compound 6a (32.1 g, 0.139 mol) was dissolved in concentrated H₂SO₄ (140mL) at 5° C. while stirring under a nitrogen atmosphere. The resultingbrown solution was treated with N-(hydroxymethyl)phthalimide (24.7 g,0.139 mol) and the mixture was slowly warmed to room temperature over 18h. The reaction mixture was slowly poured onto ice (500 g) and theresulting precipitate was isolated by filtration; 200 mL of water wasused to assist the transfer. The filter cake was added to a beaker andsuspended in 1 liter of water and 800 mL of chloroform. The mixture wasstirred while the pH was cautiously adjusted to pH 10 by the addition ofsolid Na₂CO₃ and then transferred to a separatory funnel. The layerswere separated and the basic aqueous layer was extracted twice withchloroform. The combined chloroform extracts were washed twice withbrine, dried over anhydrous K₂CO₃ and filtered. The filtrate wasconcentrated in vacuo to give 6b (50.5 g, 93%) as a yellow foam.

Step C.5′-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-spiro[piperidine-4,3′-(2H)-indole]

Compound 6b (25.0 g, 0.0642 mol) was combined with1,8-bis-(dimethylamino)naphthalene (27.5 g, 0.128 mol; CAS#20734-58-1)and dissolved in dichloroethane (320 mL) while stirring under an argonatmosphere. 1-Chloroethyl chloroformate (27.7 mL, 0.257 mol;CAS#50893-53-3) was added and the resulting black solution was heated atreflux for 2 h. The reaction mixture was cooled to room temperature andesxtracted with 3 times with 10% aq. citric acid, 3 times with saturatedaq. NaHCO₃, dried over anhydrous MgSO₄, and filtered. The filtrate wasconcentrated in vacuo to yield a reddish-brown foam.

This foam was dissolved in dry methanol (300 mL), treated with 33 mL of5.5 M HCl in isopropanol and heated at reflux while stirring under anitrogen atmosphere. After 1 h, the reaction mixture was concentrated invacuo. The resulting solid recrystallized from methanol to give thedihydrochloride salt of 6c as a brown solid. The material was slowlypartitioned between chloroform (200 mL) and 10% aq. Na₂CO₃ (150 mL). Thebasic aqueous layer was extracted twice with chloroform and the combinedorganic layers were extracted twice with 10% aq. Na₂CO₃, dried overanhydrous K₂CO₃, and filtered. The filtrate was concentrated in vacuo toafford 6c (15.0 g, 68%) s a brown solid.

Step D. 5-phenylethynyl-furan-2-carboxylic acid2,5-dioxo-pyrrolidin-1-yl ester

A solution of 5-(phenylethynyl)-2-furoic acid (10.1 g, 0.048 mmol;CAS#130423-83-5) and pyridine (26.9 mL, 0.333 mol) in acetonitrile (475mL) was treated with N,N′-disuccinimidyl carbonate (36.5 g, 0.142 mol;CAS#74124-79-1) while stirring at room temperature under a nitrogenatmosphere and the resulting slurry was stirred for 18 h. The reactionmixture was concentrated in vacuo and the residue was partitionedbetween water and DCM. The aqueous layer was extracted twice with DCMand the combined organic layers were extracted twice with 10% aq. citricacid, twice with saturated aq. NaHCO₃, dried over MgSO₄ and filtered.The filtrate was concentrated in vacuo and the residue was purified bychromatography on silica gel eluting with DCM to give 6d (13.5 g, 92%)as a white solid.

Step E.5′-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-1-(5-phenylethynyl-furan-2-yl)carbonyl-spiro[piperidine-4,3′-(2H)-indole]

Compound 6c (6.74 g, 0.0194 mol) was dissolved in THF (194 mL; warmingrequired) and treated at room temperature with 6d (8.10 g, 0.0262 mol).After 6 h, the reaction mixture was concentrated in vacuo and theresidue was portioned between EtOAc and water. The organic layer wasextracted twice with water, twice with brine, dried over anhydrousNa₂SO₄ and filtered. The filtrate was concentrated in vacuo and theresidue was purified by chromatography on silica gel eluting withheptane/EtOAc (7:3) to give 6e (8.11; 77%) as a yellow foam.

Step F.1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole](Cpd 319)

A solution of 6e (0.115 g, 0.212 mmol) and methylhydrazine (0.6 mL) inanhydrous ethanol (6 mL) was heated at 40° C. for 3 h while stirringunder argon. The reaction mixture was concentrated in vacuo and purifiedby reverse-phase HPLC eluting on a C18 column with a gradient of 10-90%acetonitrile in water containing 0.1% TFA to furnish Compound 319 (15mg, 11%) as a tan solid: MS (ES) m/z 412.2 (MH)⁺ for C₂₆H₂₅N₃O₂.

Example 71-(5-phenylethynyl-furan-2-yl)carbonyl-1′-hydroxysulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole](Cpd 327)

Step A.5′-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-hydroxysulfonyl-spiro[piperidine-4,3′-(2H)-indole](Cpd 327)

A solution of 6e (16.9 g, 0.031 mol) and triethylamine (26.1 mL, 0.187mol) in THF (312 mL) was cooled to 0° C. and treated dropwise over 30minutes with chlorosulfonic acid (3.11 mL, 0.047 mol). After 2 h at 0°C., the reaction was quenched by the addition of methanol (100 mL) andconcentrated in vacuo to give crude 7a as a brown oil.

Step B.1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-hydroxysulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole](Cpd 327)

A solution of crude 7a (0.031 mol) and methylhydrazine in anhydrousethanol (310 mL) was heated at 40° C. for 6 h while stirring under anitrogen atmosphere. The reaction mixture was concentrated in vacuo andthe residue was triturated with several portions of diethyl ether togive a yellow solid. This material was purified by reverse-phase HPLCeluting on a C18 column with a gradient of 20-50% acetonitrile in watercontaining 0.1% TFA. The fractions containing the desired product wereimmediately basified to pH 9 with concentrated NH₄OH and placed on alyophilzer. The resulting solid was triturated 4 times with hot EtOAc(250 mL) and then slurried in 1 L of methanol. Anhydrous NH₃ gas wasbubbled into the slurry over 45 minutes until a solution was achieved.The solution was filtered through a Nylon-66 (0.45μ) filter. Thefiltrate was boiled down to 250 mL and cooled to room temperature. Theresulting solid was washed with methanol and diethyl ether and thendried overnight in vacuo at 60° C. to furnish Compound 319 (10.9 g, 65%)as a beige solid: MS (ES) m/z 492.1 (MH)⁺ for C₂₆H₂₅N₃O₅S.

Example 81-(3,4-dichlorophenyl)carbonyl-2′-oxo-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole](Cpd 315)

Step A. 4-(2-bromo-4-cyano-phenylcarbamoyl)-piperidine-1-carboxylic acidtert-butyl ester

Thionyl chloride (0.028 mol, 2.0 mL) was added to a solution of1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid (0.024 mol, 5.6 g;CAS#84358-13-4), pyridine (0.060 mol, 4.9 mL), in DCM (32 mL) at 0° C.under an atmosphere of argon. After 5 min., a solution of4-amino-3-bromo-benzonitrile (0.027 mol, 5.3 g; CAS#50397-74-5), DMAP(0.037 mol, 4.5 g) in DCM (44 mL) was added to the reaction mixture andallowed to slowly warm to room temperature over 16 hrs. Triethylamine(0.047 mol, 6.6 mL) was added and the reaction mixture was refluxed for4 hours, stirred at room temperature for 16 hrs, and concentrated invacuo. The residue was dissolved in Et₂O and extracted with water (2×),1N aq. HCl (2×), saturated aq. NaHCO₃, brine, dried over Na₂SO₄,filtered and concentrated in vacuo. The resulting material was purifiedon a silica gel column eluting with heptane/EtOAc (3:2) to afford 8a asa white solid (3.2 g, 32%).

Step B.4-[(2-bromo-4-cyano-phenyl)-(4-methoxy-benzyl)-carbamoyl]-piperidine-1-carboxylicacid tert-butyl ester

A slurry of 8a (7.7 mmol, 3.2 g), 1-chloromethyl-4-methoxy-benzene (14mmol, 2.19 g, 1.9 mL) and 40 wt. % potassium fluoride on alumina (30mmol, 4.4 g) in acetonitrile (32 mL) was refluxed 6 hrs, then cooled andstirred at room temperature for 48 hrs. The reaction material wasfiltered through filter agent and the filtrate was concentrated invacuo. The resulting residue was purified by chromatography on a silicagel column eluting with heptane/EtOAc (3:2) to give 8b as a colorlesswax (3.4 g, 83%).

Step C.1-(tert-butyloxy)carbonyl-5′-cyano-2′-oxo-1′-(4-methoxybenzyl)-spiro[piperidine-4,3′-(2H)-indole]

To a solution of 8b (6.4 mmol, 3.4 g),tris(dibenzylideneacetone)dipalladium (0.64 mmol, 590 mg),racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.94 mmol, 590 mg)in dioxane (200 mL) was added sodium tert-butoxide (9.6 mmol, 930 mg).After heating at 110° C. under argon for 16 hrs, the reaction mixturewas cooled to room temperature filtered through filter agent. The filterpad was washed with DCM and the combined filtrate concentrated in vacuo.The resulting residue was taken up in DCM and extracted with 10 wt. %aq. citric acid (2×), water, saturated aq. NaHCO₃, brine, dried overNa₂SO₄, and concentrated in vacuo. The resulting residue was purified ona silica gel column eluted with 7:3 heptane/EtOAc to give 8c as a solid(1.0 g, 35%).

Step D.1-(tert-butyloxy)carbonyl-5′-cyano-2′-oxo-spiro[piperidine-4,3′-(2H)-indole]

To a solution of 8c (2.2 mmol, 1.0 g), in acetonitrile (28 mL) and water(8 mL) was added ammonium cerium(IV) nitrate (8.9 mmol, 4.9 g). Afterstirring at room temperature for 2 hrs, the reaction mixture was dilutedwith DCM, extracted with water (2×), saturated aq. NaHCO₃ (2×), brine,dried over Na₂SO₄, and concentrated in vacuo. The resulting residue waspurified on a silica gel column eluted with 3:2 EtOAc/heptane to give 8das a white solid (113 mg, 15%).

Step E.5′-cyano-1-(3,4-dichlorophenyl)carbonyl-2′-oxo-spiro[piperidine-4,3′-(2H)-indole]

To a slurry of 8d (0.39 mmol, 130 mg) in isopropyl alcohol (10 mL) wasadded 5N HCl in isopropyl alcohol (0.78 mmol, 160 μL). After 16 hrs at50° C., the reaction mixture was concentrated in vacuo. To this residuewas added 3,4-dichlorobenzoic acid (0.78 mmol, 150 mg), EDC HCl (0.78mmol, 150 mg) and DMF (5 mL). The resulting solution was stirred at roomtemperature under argon 16 hrs then quenched with water and diluted withDCM. The organic layer was separated, extracted with water, 1N aq. HCl,saturated aq. NaHCO₃ (2×), ammonium cerium(IV) nitrate (8.9 mmol, 4.9g). After stirring at room temperature for 2 hrs, the reaction mixturewas diluted with DCM, extracted with water (2×), saturated aq. NaHCO₃(2×), dried over Na₂SO₄, and concentrated in vacuo. The resultingresidue was purified on a silica gel column eluted with 1:1EtOAc/heptane to give 8e as a solid (74 mg, 47%).

Step F.1-(3,4-dichlorophenyl)carbonyl-2′-oxo-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole](Cpd 315)

A slurry of 8e (0.18 mmol, 74 mg), Raney Nickel® (14 mg) in ethylalcohol (2.5 mL) and 3N aq. NaOH (0.87 mL) was shaken under 50 psi H₂ atroom temperature for 16 hrs. The reaction mixture was filtered through anylon filter and concentrated under a stream of nitrogen. The residuewas purified on a C18 reverse-phase column eluted withacetonitrile/water/trifluoroacetic acid to and freeze-dried give thetrifluoroacetate salt of Compound 315 as a white powder (33 mg, 32%): ¹HNMR (CD₃OD) δ 7.69 (d, J=1.9 Hz, 1H), 7.66 (d, J=8.2 Hz, 1H), 7.52 (d,J=1.4 Hz, 1H), 7.43 (dd, J=1.9 Hz, J=8.2 Hz, 1H), 7.34 (dd, J=1.6 Hz,J=8.0 Hz, 1H), 6.98 (d, J=8.0 Hz, 1H), 4.32-3.9 (m, 5H), 3.70 (bm, 1H),1.95-1.85 (m, 4H); MS (ES) m/z 403.8/405.7 (MH)⁺.

Example 91-(5-phenylethynyl-furan-2-yl)carbonyl-1′-oxo-5′-aminomethyl-spiro[piperidine-4,3′-1H-isoindole](Cpd 317)

Step A. 2-bromo-4-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-benzoicacid methyl ester

A solution of methyl 2-bromo-4-(bromomethyl)benzoate (2.00 g, 6.49 mmol;CAS#128577-48-0) in DMF (65 mL) was treated with potassium phthalimide(1.32 g, 7.14 mmol) and stirred at room temperature under a nitrogenatmosphere. After 18 h, the reaction mixture was concentrated in vacuoand partitioned between EtOAc and water. The aqueous layer was extractedtwice with EtOAc and the combined organic layers were washed twice withbrine, dried over anhydrous MgSO₄ and filtered. The filtrate wasconcentrated in vacuo to give 9a (2.38 g, 98%) as a beige solid.

Step B. 2-bromo-4-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-benzoicacid

Compound 9a (1.86 g, 4.97 mmol) was combined with lithium iodide (6.65g, 49.7 mmol) in 50 mL of dry pyridine and heated at reflux whilestirring under a nitrogen atmosphere. After 2.5 days, the reactionmixture was concentrated in vacuo and the residue was suspended inwater. The pH was adjusted to pH 2 with 1N HCl and the resulting slurrywas extracted 3 times with EtOAc. The combined EtOAc extracts werewashed twice with brine, dried over anhydrous MgSO₄ and filtered. Thefiltrate was concentrated in vacuo to afford 9b (1.45 g, 81%) as beigesolid.

Step C. 4-(2,4-dimethoxy-benzylimino)-piperidine-1-carboxylic acidtert-butyl ester

A solution of 1-Boc-4-piperidone (1.05 g, 5.29 mmol; CAS#79099-07-3) and2,4-dimethoxybenzylamine (0.885 g, 5.29 mmol) in 50 mL of toluene wereheated at reflux under a nitrogen atmosphere with azeotropic removal ofwater with a Dean-Stark trap. After 16 h, the reaction mixture wascooled to room temperature and concentrated in vacuo to afford 9c (1.84g, 100%) as a light yellow oil.

Step D.4-[[2-bromo-4-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-benzoyl]-(2,4-dimethoxy-benzyl)-amino]-3,6-dihydro-2H-pyridine-1-carboxylicacid tert-butyl ester

Compound 9b (1.35 g, 3.75 mmol) was added to thionyl chloride (38 mL)and the resulting slurry was heated at reflux for 2 h while stirringunder a nitrogen atmosphere. The reaction mixture was concentrated invacuo and the residue was triturated with heptane to furnish thecorresponding acid chloride as a white solid.

The acid chloride was treated with triethylamine (2.6 mL, 18.8 mmol) andcombined with 9c (1.71 g, 4.91 mmol) in 38 mL of dry toluene. Thereaction mixture was heated at 80° C. over 18.5 h while stirring under anitrogen atmosphere. After cooling to room temperature, the reactionmixture was partitioned between water and EtOAc. The aqueous layer wasextracted twice with EtOAc and the combined organic extracts were washedtwice with brine, dried over anhydrous MgSO₄ and filtered. The filtratewas concentrated in vacuo and the residue was purified by chromatographyon silica gel eluting with 30-70% EtOAc in heptane to give 9d (2.11 g,82%) as a white foam.

Compound 9d (1.50 g, 2.17 mmol, triicyclopentylphosphine (1.46 g, 5.21mmol; CAS#7650-88-6), and dicyclohexylamine (6.90 mL, 32.5 mmol) andpalladium(II) acetate (585 mg, 2.61 mmol) were dissolved inN,N-dimethylacetamide (22 mL) and heated at 100° C. in a sealed tube for7 days. The reaction mixture was cooled to room temperature, dilutedwith methanol (22 mL) and filtered through filter agent. The filtratewas concentrated in vacuo and partitioned between EtOAc and 10% aq.citric acid. The organic layer was extracted twice with 10% aq. citricacid, twice with brine, dried over anhydrous MgSO₄ and filtered. Thefiltrate was concentrated in vacuo and the residue was purified bychromatography on silica gel eluting with 60-80% EtOAc in hexane to give9e (0.65 g, 49%) was a white foam.

Step G.5′-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-1′-oxo-spiro[piperidine-4,3-1H-isoindole]

A solution of 9f (0.64 g, 1.05 mmol) in 20 mL of a 4:1 mixture of DCMand TFA was stirred at room temperature for 45 minutes. The reactionmixture was concentrated in vacuo and the residue was triturated 3 timeswith diethyl ether to provide a white solid. This material was dissolvedin anhydrous ethanol (20 mL) and combined with 10% palladium on carbon(0.51 g) and placed on Parr hydrogenator under 50 psig of hydrogen.After 36 h, the reaction mixture was filtered first through filter agentand then through a Nylon-66 (0.45μ) filter. The filtrate wasconcentrated in vacuo and the residue was partitioned between EtOAc and10% aq. Na₂CO₃. The organic layer was extracted twice with 10% aq.Na₂CO₃, twice with brine, dried over anhydrous K₂CO₃ and filtered. Thefiltrate was concentrated in vacuo to give 9g as a white foam.

Step H.5′-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-1-(5-Phenylethynyl-furan-2-yl)carbonyl-1′-oxo-spiro[piperidine-4,3′-1H-isoindole]

A solution of 9g (0.200 g, 0.391 mmol), 5-(2-phenyleth-1-ynyl-2-furoicacid, 0.091 g, 0.430 mmol) and DIPEA (0.204 mL, 1.17 mmol) in dry DCM (5mL) was treated with BOP-Cl (0.119 g, 0.469 mmol) while stirring at roomtemperature under a nitrogen atmosphere. After 1.5 h, the reactionmixture was extraxcted 3 times with 10% aq. citric acid, 3 times withsaturated aq. NaHCO₃, 3 times with brine, dried over anhydrous MgSO₄ andfiltered. The filtrate was concentrated in vacuo to afford 9 h (0.282 g,100%) as a white solid.

Step I.5′-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-1-(5-Phenylethynyl-furan-2-yl)carbonyl-1′-oxo-spiro[piperidine-4,3′-1H-isoindole]

Compound 9h (0.268 g, 0.380 mmol) was slurried in TFA (10 mL) andstirred at room temperature under a nitrogen atmosphere for 22 h. Thereaction mixture was concentrated in vacuo. The residue was partitionedbetween saturated aq. NaHCO₃ and DCM. The organic layer was extractedtwice with saturated aq. NaHCO₃, twice with brine, dried over anhydrousMgSO₄ and filtered. The filtrate was concentrated in vacuo to furnish 91(0.094 g, 45%) as a tan solid.

Step I.1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-oxo-5′-aminomethyl-spiro[piperidine-4,3′-1H-isoindole](Cpd 317)

Compound 9i (47 mg, 0.0856 mmol) was dissolved in 10:1 mixture ofethanol and methylhydrazine at heated at 40° C. for 3 h. The reactionmixture was concentrated in vacuo and purified by reverse-phase HPLCeluting on a C18 column with a gradient of 20-80% acetonitrile in watercontaining 0.1% TFA to furnish Compound 317 (34 mg, 71%) as a tan solid:MS (ES) m/z 426.3 (MH)⁺ for C₂₆H₂₃N₃O₃.

Biological Examples β-Tryptase In-Vitro Enzyme Assay

The β-tryptase assay was conducted with human lung tryptase (CortexBiochem #CP3033) in an aqueous buffer (10 mM Tris, 10 mM Hepes, 150 mMNaCl, 0.1% PEG 8000, pH 7.4) using the chromogenic substrateH-D-HHT-Ala-Arg-pNa.2AcOH (American Diagnostica #238)/Km 580 μM) and amicroplate reader (Molecular Devices). IC₅₀ experiments were conductedby fixing the enzyme and substrate concentrations (1 nM [E]/500 μM [S])and varying the inhibitor concentration. Changes in absorbance at 405 nmwere monitored using the software program Softmax Pro (MolecularDevices), upon addition of enzyme without inhibition at room temperaturefor 15 min. Percent inhibition was calculated by comparing the initialreaction velocity of samples without inhibitor to those with inhibitor.The initial reaction velocities were analyzed using Microsoft Excel.

TABLE 1 Tryptase IC₅₀, (μM) <0.01 μM; <0.05 μM; <1.0 μM; <5.0 μM CpdIC₅₀ Cpd IC₅₀ Cpd IC₅₀ 1 0.031 121 0.51 241 0.0051 2 1.4 122 0.76 2420.65 3 0.0035 123 0.69 243 3.1 4 0.75 124 1.1 244 2.5 5 0.45 125 7.5 2450.51 6 5.8 126 0.15 246 0.20 7 0.78 127 3.7 247 0.036 8 3.4 128 0.17 2480.33 9 3.3 129 0.099 249 0.83 10 3.0 130 0.028 250 0.44 11 4.7 131 0.072251 1.5 12 0.066 132 0.026 252 1.6 13 1.1 133 0.081 253 2.4 14 3.7 1340.076 254 0.37 15 5.5 135 0.33 255 0.58 16 0.43 136 0.025 256 0.82 170.29 137 0.053 257 0.44 18 3.3 138 0.14 258 0.028 19 0.56 139 0.087 2590.055 20 0.14 140 0.040 260 1.2 21 0.51 141 0.48 261 0.073 22 2.1 1420.65 262 4.5 23 0.090 143 0.056 263 5.1 24 0.15 144 0.030 264 3.2 250.14 145 0.34 265 0.87 26 0.23 146 0.0052 266 0.20 27 0.034 147 0.066267 0.34 28 0.12 148 0.33 268 2.9 29 0.13 149 0.11 269 1.0 30 0.14 1500.18 270 6.4 31 0.055 151 0.18 271 2.8 32 0.041 152 0.0023 272 0.19 330.43 153 0.0012 273 1.2 34 0.020 154 0.26 274 6.4 35 0.0043 155 0.012275 0.022 36 0.82 156 0.13 276 0.15 37 0.73 157 0.017 277 0.0060 38 0.65158 4.5 278 0.012 39 3.7 159 0.21 279 8.0 40 0.25 160 0.21 280 0.22 410.47 161 0.053 281 0.024 42 0.36 162 0.079 282 0.70 43 0.25 163 0.054283 0.91 44 0.23 164 0.14 284 0.0046 45 0.22 165 0.38 285 0.36 46 0.11166 0.071 286 0.92 47 0.82 167 0.60 287 4.3 48 0.016 168 0.048 288 0.2849 0.13 169 1.6 289 1.4 50 0.036 170 0.0083 290 0.16 51 0.19 171 0.17291 0.40 52 0.022 172 0.0072 292 6.1 53 0.87 173 0.013 293 1.2 54 0.75174 0.017 294 0.097 55 1.0 175 0.058 295 0.042 56 0.19 176 0.041 2960.21 57 0.18 177 0.026 297 9.6 58 0.71 178 0.44 298 0.21 59 0.36 1790.26 299 0.017 60 2.1 180 0.78 300 1.5 61 7.5 181 1.7 301 1.5 62 0.80182 0.74 302 0.75 63 0.041 183 5.8 303 0.0037 64 0.095 184 0.21 3040.030 65 0.0045 185 1.5 305 6.3 66 1.9 186 0.053 306 0.071 67 4.8 1870.79 307 0.060 68 0.19 188 0.13 308 7.3 69 1.6 189 0.38 309 0.10 70 0.15190 0.59 310 0.78 71 0.91 191 0.25 311 0.039 72 0.52 192 0.15 312 0.5973 2.5 193 0.36 313 0.14 74 0.16 194 0.15 314 1.3 75 0.47 195 0.12 3150.48 76 0.42 196 0.68 316 0.074 77 0.10 197 0.23 317 0.0073 78 1.4 1980.073 318 0.0031 79 1.4 199 0.18 319 0.026 80 2.7 200 4.1 320 0.28 812.3 201 0.045 321 0.16 82 1.3 202 0.051 322 0.45 83 4.3 203 0.28 3230.11 84 1.4 204 0.089 324 0.20 85 2.7 205 0.74 325 0.025 86 0.62 2060.26 326 0.47 87 1.7 207 1.5 327 0.018 88 0.026 208 0.012 328 0.29 891.4 209 0.33 329 0.044 90 0.98 210 0.026 330 0.025 91 0.48 211 0.017 3310.041 92 0.49 212 0.37 332 0.028 93 0.35 213 0.24 333 0.065 94 0.24 2140.0065 334 0.047 95 3.2 215 0.76 335 0.020 96 0.45 216 1.7 336 0.028 971.5 217 0.65 337 0.036 98 1.7 218 0.008 338 0.073 99 0.58 219 0.0029 3390.015 100 0.68 220 0.69 340 0.0018 101 12.4 221 0.55 341 0.0057 102 0.60222 0.26 342 0.0052 103 0.96 223 0.021 343 0.023 104 4.5 224 0.28 3440.023 105 0.77 225 0.047 345 0.013 106 0.61 226 3.2 346 0.040 107 0.082227 0.044 347 0.024 108 0.25 228 0.037 348 0.024 109 0.21 229 0.0053 3490.016 110 0.037 230 0.14 350 0.025 111 0.19 231 0.091 351 0.068 112 0.18232 0.015 352 5.3 113 0.13 233 0.082 353 0.037 114 0.24 234 0.0095 3540.43 115 0.24 235 0.0092 355 0.29 116 0.29 236 0.75 356 0.18 117 0.60237 0.27 357 0.28 118 0.11 238 0.21 358 0.026 119 1.4 239 0.27 359 0.015120 0.13 240 0.0018

Sheep Efficacy Model In-Vivo Efficacy Assays

The in vivo efficacy of Compound 3 was evaluated in antigen-inducedallergic sheep, which is a well-characterized asthma model (Abraham, W.M. Pulmonary Pharmacol. 1989, 2, 33-40). Compound 3 was administered viaoral gavage to two sheep previously shown to be allergic responders toinhaled Ascaris suum antigen (FIG. 1). The compound was given at a doseof 30 mg/kg, BID, on day 1, and again on day 2 at 2 h prior to antigenchallenge and then 4 h after antigen challenge. Airway resistance(SR_(L)) was monitored for 8 h post antigen challenge and airwayhyper-reactivity to carbachol (PC₄₀₀) was measured 24 h post antigenchallenge. The changes in specific airway resistance (SRL) during theearly phase (EP) is shown in FIG. 1. The late phase (LP) responses andairway hyperreactivity in response to antigen challenge is shown in FIG.2. The results demonstrate that Compound 3 completely blocked the lateresponse (LP; 4-8 h post antigen) and the increase in airwayhyper-reactivity at 24 h, but did not effect a change in acute earlyphase response (EP; 0-4 h) post antigen.

Guinea Pig Efficacy Model.

The in vivo efficacy of Compound 3 was evaluated in a guinea pig modelof allergic asthma. In this model, guinea pigs were sensitized andchallenged with chicken egg ovalbumin (OVA) according to the protocol ofN. Smith and F. J. Johnson (Clin. Exp. Allergy 2005, 35, 522-530), withsome slight modifications. Guinea pigs were sensitized with 80 mg of OVAand 80 mg of aluminum hydroxide administered intraperitoneally on day 0,then challenged with 0.03% OVA aerosol for 10 minutes on day 14. In theexperiment measuring early phase pulmonary response (EAR), guinea pigswere challenged for an additional three minutes with 0.06% OVA aerosol.EAR was measured as enhanced pause (PenH) using BUXCO whole bodyplethysmography for 10 minutes immediately following the OVA aerosolchallenge. The animals were then euthanized and assessed forbronchoalveolar lavage (BAL) immune cell counts 24 hours after aerosolchallenge on day 15. Either Compound 3 in doses of 3, 10, and/or 30mg/kg or vehicle were administered subcutaneously, 1-2 hours before and4-6 hours after OVA aerosol challenge.

As shown in FIG. 3, when Compound 3 was administered at 30 mg/kg, itproduced a greater than 93% reduction in EAR as measured with whole bodyplethysmography (in PenH) relative to sensitized and challenged guineapigs treated with vehicle (positive control group). As shown in FIG. 4,when administered at dose levels of 3, 10 and 30 mg/kg, Compound 3 alsoproduced a dose-dependent reduction in the total and eosinophilic BALcell counts with the highest dose (30 mg/kg) producing a 66% reductionin BAL eosinophils (EAR and BAL samples per group ranged from 5 to 18;values represent the mean±SEM; * represents p value of ≦0.005).

Throughout this application, various publications are cited. Thedisclosure of these publications is hereby incorporated by referenceinto this application to describe more fully the state of the art towhich this invention pertains.

While the foregoing specification teaches the principles of the presentinvention, with examples provided for the purpose of illustration, itwill be understood that the practice of the invention encompasses all ofthe usual variations, adaptations and modifications as come within thescope of the following claims and their equivalents.

1. A compound of Formula (I):

or a form thereof, wherein X₁ and X₂, respectively, are selected from the group consisting of —CH₂— and —CH₂—, —CH₂— and —O—, —O— and —CH₂—, —CH₂— and —N(R₄)—, —N(R₄)— and —CH₂—, —CH₂— and —S—, —S— and —CH₂—, —CH₂— and —S(O)—, —S(O)— and —CH₂—, —CH₂— and —SO₂—, —SO₂— and —CH₂—, —C(O)— and —CH₂—, —CH₂— and —C(O)—, —C(O)— and —N(R₄)—, —N(R₄)— and —C(O)—, —C(O)— and —S— and —S— and —C(O)—; X₃ and X₄, respectively, are selected from the group consisting of —CH₂— and —CH₂—, —CH₂— and —C(O)— and —C(O)— and —CH₂—; R₁ is selected from the group consisting of aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl, (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl, (C₁₋₄alkyl)₃-aminoC₁₋₄alkyl, formylaminoC₁₋₄alkyl, arylcarbonylaminoC₁₋₄alkyl, aminosulfonylaminoC₁₋₄alkyl, arylC₁₋₄alkylaminoC₁₋₄alkyl, C₃₋₁₄cycloalkylcarbonylaminoC₁₋₄alkyl, C₃₋₁₄cycloalkylC₁₋₄alkenylcarbonylaminoC₁₋₄alkyl, arylC₁₋₄alkylcarbonylaminoC₁₋₄alkyl, arylC₂₋₄alkenylcarbonylaminoC₁₋₄alkyl, arylC₂₋₄alkynylcarbonylaminoC₁₋₄alkyl, arylsulfonylaminoC₁₋₄alkyl, heterocyclylcarbonylaminoC₁₋₄alkyl, heterocyclylC₁₋₄alkylcarbonylaminoC₁₋₄alkyl, heterocyclylC₁₋₄alkenylcarbonylaminoC₁₋₄alkyl, heteroarylcarbonylaminoC₁₋₄alkyl, heteroarylC₂₋₄alkenylcarbonylaminoC₁₋₄alkyl, aminoimino, hydroxyaminoimino, (C₁₋₄alkyl)aminoimino, (C₁₋₄alkyl)₂-aminoimino and aminoaminoimino, wherein each instance of aryl is optionally substituted with one or two halogen substituents; R₂ is absent or is one halogen substituent; R³ is hydrogen or is selected from the group consisting of R⁵-arylC₁₋₄alkyl, carbonyl and sulfonyl, wherein carbonyl and sulfonyl are each substituted with a substituent selected from the group consisting of R⁵-aryl, R⁵-arylC₁₋₄alkyl, R⁵-arylC₁₋₄alkylamino, (R⁵-aryl)₁₋₂C₁₋₄alkyl, R⁵-arylC₂₋₄alkenyl, R⁵-arylC₂₋₄alkynyl, R⁸—C₃₋₁₄cycloalkyl, R⁸—C₃₋₁₄cycloalkylC₁₋₄alkyl, R⁸—C₃₋₁₄cycloalkylC₁₋₄alkenyl, R⁷-heterocyclyl, R⁷-heterocyclylC₁₋₄alkyl, R⁷-heterocyclylC₁₋₄alkenyl, R⁸-heteroaryl and R⁸-heteroarylC₂₋₄alkenyl, wherein each instance of C₂₋₄alkenyl is optionally substituted with one substituent selected from the group consisting of halogen, cyano, C₁₋₄alkylcarbonylamino and aryl; R⁵ is one optional substituent selected from the group consisting of R^(5a)-aryl, R^(5a)-arylC₁₋₄alkyl, R^(5a)-arylC₁₋₄alkoxy, R^(5a)-aryloxy, R^(5a)-arylcarbonyl, R^(5a)-arylsulfonylamino, R^(5b)-heteroaryl, R^(5b)-heteroarylC₁₋₄alkyl, R^(5b)-heteroarylC₁₋₄alkylcarbonylamino, R^(5b)-heteroarylthio, R^(5b)-heteroaryl-(R^(5b))-heteroaryl, R^(5b)-heterocyclyl and C₃₋₁₄cycloalkyl, and one or two optional substituents each selected from the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl, C₂₋₄alkenyl, C₂₋₄alkynyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, C₁₋₄alkoxyC₁₋₄alkyl, C₁₋₄alkoxyC₁₋₄alkoxy, haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio, C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, aminothiocarbonylamino, amino, (C₁₋₄alkyl)amino, (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl, (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl, aminocarbonyl, C₁₋₄alkylsulfonyl, aminosulfonyl, (C₁₋₄alkyl)aminosulfonyl and (C₁₋₄alkyl)₂-aminosulfonyl; R^(5a) is one, two or three optional substituents each selected from the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio, amino, (C₁₋₄alkyl)amino, (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl and (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl; R^(5b) is one, two or three optional substituents each selected from the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio, amino, (C₁₋₄alkyl)amino, (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl and (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl; R⁶ is one or two optional substituents each selected from the group consisting of C₁₋₄alkyl, oxo and aryl; R⁷ is an optional substituent on one, two or three carbon atoms each selected from the group consisting of halogen, C₁₋₄alkyl, C₁₋₄alkoxy, C₁₋₄alkylthio, arylC₁₋₄alkylthio, oxo and aryl, and two optional substituents on one carbon atom each selected from the group consisting of C₁₋₄alkyl and halogen, and one or two optional oxo substituents on a sulfur atom, when said sulfur atom is present; R⁸ is an optional substituent on one carbon atom or an available nitrogen atom selected from the group consisting of R^(8a)-aryl, R^(8a)-arylC₁₋₄alkyl, R^(8a)-arylC₂₋₄alkenyl, R^(8a)-arylC₂₋₄alkynyl, R^(8a)-aryloxy, R^(8a)-aryloxyC₁₋₄alkyl, R^(8a)-arylthio, R^(8a)-arylC₁₋₄alkylthio, R^(8a)-arylC₁₋₄alkylthioC₁₋₄alkyl, R^(8a)-arylsulfonyl, R^(8b)-heteroaryl, R^(8b)-heteroarylC₁₋₄alkyl, R^(8b)-heteroarylthioC₁₋₄alkyl, R^(8b)-heteroarylcarbonylaminoC₁₋₄alkyl and R^(8c)-heterocyclylC₁₋₄alkyl, and an optional C₁₋₄alkyl substituent on an available nitrogen atom, and an optional substituent on one, two or three carbon atoms each selected from the group consisting of halogen, cyano, C₁₋₄alkyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, haloC₁₋₄alkoxy, formyl, C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, C₁₋₄alkylthio and C₁₋₄alkylsulfonyl; R^(8a) is one, two or three optional substituents each selected from the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl, C₂₋₄alkenyl, C₂₋₄alkynyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio, C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, amino, (C₁₋₄alkyl)amino, (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl and (C₁₋₄alkyl)₂ aminoC₁₋₄alkyl; R^(8b) is one, two or three optional substituents each selected from the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl, C₂₋₄alkenyl, C₂₋₄alkynyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio, C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, amino, (C₁₋₄alkyl)amino, (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl and (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl; R₄ is one substituent selected from the group consisting of hydrogen, C₁₋₄alkyl, carboxyC₁₋₄alkyl, C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, C₁₋₄alkoxycarbonylC₁₋₄alkyl, C₁₋₄alkoxycarbonylC₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonylcarbonyl, aminocarbonyl, R⁹-arylC₁₋₄alkyl, R⁹-arylcarbonyl, hydroxysulfonyl, aminosulfonyl, C₁₋₄alkylsulfonyl, hydroxysulfonylC₁₋₄alkylcarbonyl, C₁₋₄alkylsulfonylC₁₋₄alkylcarbonyl, C₁₋₄alkylsulfonylC₁₋₄alkylsulfonyl, C₁₋₄alkoxycarbonylC₁₋₄alkylsulfonyl, R⁹-arylsulfonyl, P[(O)(OH)₂]-C₁₋₄alkyl, R¹⁰-heterocyclylcarbonyl, R¹⁰-heterocyclylsulfonyl, R¹¹-heteroarylcarbonyl, R¹¹-heteroarylC₁₋₄alkylcarbonyl and R¹¹-heteroarylsulfonyl, wherein C₁₋₄alkoxycarbonylC₁₋₄alkylcarbonyl is optionally substituted on C₁₋₄alkyl with (C₁₋₄alkyl)aminoamino; R⁹ is one or two optional substituents each selected from the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl, C₂₋₄alkenyl, C₂₋₄alkynyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, carboxy, C₁₋₄alkoxyC₁₋₄alkyl, C₁₋₄alkoxyC₁₋₄alkoxy, haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio, C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, aminothiocarbonylamino, amino, (C₁₋₄alkyl)amino, (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl, (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl, aminocarbonyl, C₁₋₄alkylsulfonyl, aminosulfonyl, (C₁₋₄alkyl)aminosulfonyl and (C₁₋₄alkyl)₂-aminosulfonyl; R¹⁰ is an optional substituent on one, two or three carbon atoms each selected from the group consisting of halogen, C₁₋₄alkyl, C₁₋₄alkoxy, C₁₋₄alkylthio, (C₁₋₄alkyl)aminoamino and oxo, and two optional substituents on one carbon atom each selected from the group consisting of C₁₋₄alkyl and halogen, and one or two optional oxo substituents on a sulfur atom, when said sulfur atom is present; and R¹¹ is an optional C₁₋₄alkyl substituent on an available nitrogen atom, and an optional substituent on one, two or three carbon atoms each selected from the group consisting of halogen, cyano, C₁₋₄alkyl, C₁₋₄alkoxy, haloC₁₋₄alkoxy, carboxy, formyl, C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl and C₁₋₄alkylthio.
 2. The compound of claim 1, wherein X₁ and X₂, respectively, are selected from the group consisting of —CH₂— and —CH₂—, —CH₂— and —O—, —O— and —CH₂—, —CH₂— and —N(R₄)—, —N(R₄)— and —CH₂—, —CH₂— and —S—, —S— and —CH₂₋₃—CH₂— and —S(O)—, —S(O)— and —CH₂—, —CH₂— and —SO₂—, —SO₂— and —CH₂—, —C(O)— and —CH₂—, —CH₂— and —C(O)—, —C(O)— and —N(R₄)—, —N(R₄)— and —C(O)—, —C(O)— and —S— and —S— and —C(O)—; X₃ and X₄, respectively, are selected from the group consisting of —CH₂— and —CH₂—, —CH₂— and —C(O)— and —C(O)— and —CH₂—; R₁ is selected from the group consisting of aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl, (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl, (C₁₋₄alkyl)₃-aminoC₁₋₄alkyl, formylaminoC₁₋₄alkyl, phenylcarbonylaminoC₁₋₄alkyl, aminosulfonylaminoC₁₋₄alkyl, arylC₁₋₄alkylaminoC₁₋₄alkyl, C₃₋₁₄cycloalkylcarbonylaminoC₁₋₄alkyl, C₃₋₁₄cycloalkylC₁₋₄alkenylcarbonylaminoC₁₋₄alkyl, arylC₁₋₄alkylcarbonylaminoC₁₋₄alkyl, arylC₂₋₄alkenylcarbonylaminoC₁₋₄alkyl, arylC₂₋₄alkynylcarbonylaminoC₁₋₄alkyl, arylsulfonylaminoC₁₋₄alkyl, heterocyclylcarbonylaminoC₁₋₄alkyl, heterocyclylC₁₋₄alkylcarbonylaminoC₁₋₄alkyl, heterocyclylC₁₋₄alkenylcarbonylaminoC₁₋₄alkyl, heteroarylcarbonylaminoC₁₋₄alkyl, heteroarylC₂₋₄alkenylcarbonylaminoC₁₋₄alkyl, aminoimino, hydroxyaminoimino, (C₁₋₄alkyl)aminoimino, (C₁₋₄alkyl)₂-aminoimino and aminoaminoimino, wherein each instance of phenyl is optionally substituted with one or two halogen substituents; R₂ is absent or is one halogen substituent; R³ is hydrogen or is selected from the group consisting of R⁵-phenylC₁₋₄alkyl, carbonyl and sulfonyl, wherein carbonyl and sulfonyl are each substituted with a substituent selected from the group consisting of R⁵-phenyl, R⁵-naphthalenyl, R⁵-phenyl-C₁₋₄alkyl, R⁵-naphthalenyl-C₁₋₄alkyl, R⁶-fluorenyl-C₁₋₄alkyl, R⁵-phenyl-C₁₋₄alkylamino, (R⁵-phenyl)₁₋₂C₁₋₄alkyl, R⁵-phenyl-C₂₋₄alkenyl, R⁵-naphthalenyl-C₂₋₄alkenyl, R⁵-phenylC₂₋₄alkynyl, R⁶-cyclopropyl, R⁶-indanyl, R⁶-1H-indenyl, R⁶-9H-fluorenyl, R⁶—C₃₋₁₄cycloalkylC₁₋₄alkyl, R⁶-9H-fluorenyl-C₁₋₄alkenyl, R⁷-benzo[1,3]dioxolyl, R⁷-4,5-dihydro-benzo[c]thiophenyl, R⁷-4,5,6,7-tetrahydro-benzo[c]thiophenyl, R⁷-4,5,6,7-tetrahydro-benzo[b]thiophenyl, R⁷-chromenyl, R⁷-9H-xanthenyl, R⁷-9H-thioxanthenyl, R⁷-5,6-dihydro-4H-cyclopenta[b]thiophenyl, R⁷-4,5,6,7-tetrahydro-benzofuranyl, R⁷-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophenyl, R⁷-spiro[cyclohexane-1,6′-5,7-dihydro-4H-benzo[b]thiophene], R⁷-benzo[1,3]dioxolyl-C₁₋₄alkyl, R⁷-benzo[1,3]dioxolyl-C₁₋₄alkenyl, R⁷-3H-isobenzofuranyl-C₁₋₄alkenyl, R⁸-furanyl, R⁸-thienyl, R⁸-thiazolyl, R⁸-[1,2,3]thiadiazolyl, R⁸-pyridinyl, R⁸-1H-indolyl, R⁸-benzo[b]furanyl, R⁸-benzo[b]thiophenyl, R⁸-benzo[c]thiophenyl, R⁸-1H-benzoimidazolyl, R⁸-benzothiazolyl, R⁸-thieno[3,2-b]thiophenyl, R⁸-thieno[2,3-b]thiophenyl, R⁸-naphtho[2,1-b]thiophenyl, R⁸-1H-thieno[2,3-c]pyrazolyl, R⁸-imidazo[1,2-a]pyridinyl, R⁸-1H-imidazolyl-C₂₋₄alkenyl, R⁸-furanyl-C₂₋₄alkenyl, R⁸-thienyl-C₂₋₄alkenyl and R⁸-pyridinyl-C₂₋₄alkenyl, wherein each instance of C₂₋₄alkenyl is optionally substituted with one substituent selected from the group consisting of halogen, cyano, C₁₋₄alkylcarbonylamino and aryl; R⁵ is one optional substituent selected from the group consisting of R^(5a)-phenyl, R^(5a)-phenylC₁₋₄alkyl, R^(5a)-phenylC₁₋₄alkoxy, R^(5a)-phenoxy, R^(5a)-phenylcarbonyl, R^(5a)-phenylsulfonylamino, R^(5b)-heteroaryl, R^(5b)-1H-benzoimidazolyl-C₁₋₄alkyl, R^(5b)-1H-benzoimidazolyl-C₁₋₄alkylcarbonylamino, R^(5b)-thienyl-C₁₋₄alkylcarbonylamino, R^(5b)-pyrimidinylthio, R^(5b)-benzoxazolyl-(R^(5b))-pyrazolyl, R^(5b)-thienyl-(R^(5b))-[1,2,4]oxadiazolyl, R^(5b)-benzo[1,3]dioxolyl and cyclohexyl, and one or two optional substituents each selected from the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl, C₂₋₄alkenyl, C₂₋₄alkynyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, C₁₋₄alkoxyC₁₋₄alkyl, C₁₋₄alkoxyC₁₋₄alkoxy, haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio, C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, aminothiocarbonylamino, amino, (C₁₋₄alkyl)amino, (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl, (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl, aminocarbonyl, C₁₋₄alkylsulfonyl, aminosulfonyl, (C₁₋₄alkyl)aminosulfonyl and (C₁₋₄alkyl)₂-aminosulfonyl; R^(5a) is one, two or three optional substituents each selected from the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio, amino, (C₁₋₄alkyl)amino, (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl and (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl; R^(5b) is one, two or three optional substituents each selected from the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio, amino, (C₁₋₄alkyl)amino, (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl and (C₁₋₄alkyl)₂ aminoC₁₋₄alkyl; R⁶ is one or two optional substituents each selected from the group consisting of C₁₋₄alkyl, oxo and phenyl; R⁷ is an optional substituent on one, two or three carbon atoms each selected from the group consisting of halogen, C₁₋₄alkyl, C₁₋₄alkoxy, C₁₋₄alkylthio, phenylC₁₋₄alkylthio, oxo and phenyl, and two optional substituents on one carbon atom each selected from the group consisting of C₁₋₄alkyl and halogen, and one or two optional oxo substituents on a sulfur atom, when said sulfur atom is present; R⁸ is an optional substituent on one carbon atom or an available nitrogen atom selected from the group consisting of R^(8a)-phenyl, R^(8a)-phenylC₁₋₄alkyl, R^(8a)-phenylC₂₋₄alkenyl, R^(8a)-phenylC₂₋₄alkynyl, R^(8a)-naphthalenylC₂₋₄alkynyl, R^(8a)-phenoxy, R^(8a)-phenoxyC₁₋₄alkyl, R^(8a)-phenylthio, R^(8a)-phenylC₁₋₄alkylthio, R^(8a)-phenylC₁₋₄alkylthioC₁₋₄alkyl, R^(8a)-phenylsulfonyl, R^(8b)-pyridinyl, R^(8b)-pyrazolyl, R^(8b)-thienyl, R^(8b)-thiazolyl, R^(8b)-pyrazolylC₁₋₄alkyl, R^(8b)-pyrimidinylthioC₁₋₄alkyl, R^(8b)-furanylcarbonylaminoC₁₋₄alkyl and R^(8c)-morpholinylC₁₋₄alkyl, and an optional C₁₋₄alkyl substituent on an available nitrogen atom, and an optional substituent on one, two or three carbon atoms each selected from the group consisting of halogen, cyano, C₁₋₄alkyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, haloC₁₋₄alkoxy, formyl, C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, C₁₋₄alkylthio and C₁₋₄alkylsulfonyl; R^(8a) is one, two or three optional substituents each selected from the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl, C₂₋₄alkenyl, C₂₋₄alkynyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio, C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, amino, (C₁₋₄alkyl)amino, (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl and (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl; R^(8b) is one, two or three optional substituents each selected from the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl, C₂₋₄alkenyl, C₂₋₄alkynyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio, C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, amino, (C₁₋₄alkyl)amino, (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl and (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl; R₄ is one substituent selected from the group consisting of hydrogen, C₁₋₄alkyl, carboxyC₁₋₄alkyl, C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, C₁₋₄alkoxycarbonylC₁₋₄alkyl, C₁₋₄alkoxycarbonylC₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonylcarbonyl, aminocarbonyl, R⁹-phenyl-C₁₋₄alkyl, R⁹-phenyl-carbonyl, hydroxysulfonyl, aminosulfonyl, C₁₋₄alkylsulfonyl, hydroxysulfonylC₁₋₄alkylcarbonyl, C₁₋₄alkylsulfonylC₁₋₄alkylcarbonyl, C₁₋₄alkylsulfonylC₁₋₄alkylsulfonyl, C₁₋₄alkoxycarbonylC₁₋₄alkylsulfonyl, R⁹-phenyl-sulfonyl, P[(O)(OH)₂]—C₁₋₄alkyl, R¹⁰-tetrahydrothienyl-sulfonyl, R¹¹-1H-tetrazolyl-carbonyl, R¹¹-1H-tetrazolyl-C₁₋₄alkylcarbonyl, R¹¹-1H-imidazolyl-sulfonyl, R¹¹-furanyl-sulfonyl and R¹¹-thienyl-sulfonyl, wherein C₁₋₄alkoxycarbonylC₁₋₄alkylcarbonyl is optionally substituted on C₁₋₄alkyl with (C₁₋₄alkyl)aminoamino; R⁹ is one or two optional substituents each selected from the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl, C₂₋₄alkenyl, C₂₋₄alkynyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, carboxy, C₁₋₄alkoxyC₁₋₄alkyl, C₁₋₄alkoxyC₁₋₄alkoxy, haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio, C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, aminothiocarbonylamino, amino, (C₁₋₄alkyl)amino, (C₁₋₄alkyl)₂-amino, aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl, (C₁₋₄alkyl)₂-aminoC₁₋₄alkyl, aminocarbonyl, C₁₋₄alkylsulfonyl, aminosulfonyl, (C₁₋₄alkyl)aminosulfonyl and (C₁₋₄alkyl)₂-aminosulfonyl; R¹⁰ is an optional substituent on one, two or three carbon atoms each selected from the group consisting of halogen, C₁₋₄alkyl, C₁₋₄alkoxy, C₁₋₄alkylthio, (C₁₋₄alkyl)aminoamino and oxo, two optional substituents on one carbon atom each selected from the group consisting of C₁₋₄alkyl and halogen, and one or two optional oxo substituents on a sulfur atom, when said sulfur atom is present; R¹¹ is an optional C₁₋₄alkyl substituent on an available nitrogen atom, and an optional substituent on one, two or three carbon atoms each selected from the group consisting of halogen, cyano, C₁₋₄alkyl, C₁₋₄alkoxy, haloC₁₋₄alkoxy, carboxy, formyl, C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl and C₁₋₄alkylthio.
 3. The compound of claim 1, wherein X₁ and X₂, respectively, are selected from the group consisting of —CH₂— and —CH₂—, —CH₂— and —O—, —CH₂— and —N(R₄)—, —CH₂— and —S—, —C(O)— and —N(R₄)— and —N(R₄)— and —C(O)—; X₃ and X₄, respectively, are —CH₂— and —CH₂—; R₁ is selected from the group consisting of aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl, formylaminoC₁₋₄alkyl, arylcarbonylaminoC₁₋₄alkyl, aminoimino, hydroxyaminoimino, (C₁₋₄alkyl)aminoimino, (C₁₋₄alkyl)₂-aminoimino and aminoaminoimino, wherein each instance of aryl is optionally substituted with one or two halogen substituents; R₂ is absent or is one halogen substituent; R³ is hydrogen or is selected from the group consisting of R⁵-arylC₁₋₄alkyl, carbonyl and sulfonyl, wherein carbonyl and sulfonyl are each substituted with a substituent selected from the group consisting of R⁵-aryl, R⁵-arylC₁₋₄alkyl, R⁵-arylC₁₋₄alkylamino, (R⁵-aryl)₁₋₂C₁₋₄alkyl, R⁵-arylC₂₋₄alkenyl, R⁵-arylC₂₋₄alkynyl, R⁸—C₃₋₁₄cycloalkyl, R⁸—C₃₋₁₄cycloalkylC₁₋₄alkyl, R⁸—C₃₋₁₄cycloalkylC₁₋₄alkenyl, R⁷-heterocyclyl, R⁷-heterocyclylC₁₋₄alkyl, R⁷-heterocyclylC₁₋₄alkenyl, R⁸-heteroaryl and R⁸-heteroarylC₂₋₄alkenyl, wherein each instance of C₂₋₄alkenyl is optionally substituted with one substituent selected from the group consisting of halogen, cyano, C₁₋₄alkylcarbonylamino and aryl; R⁵ is one optional substituent selected from the group consisting of R^(5a)-aryl, R^(5a)-arylC₁₋₄alkyl, R^(5a)-arylC₁₋₄alkoxy, R^(5a)-aryloxy, R^(5a)-arylcarbonyl, R^(5a)-arylsulfonylamino, R^(5b)-heteroaryl, R^(5b)-heteroarylC₁₋₄alkyl, R^(5b)-heteroarylC₁₋₄alkylcarbonylamino, R^(5b)-heteroarylthio, R^(5b)-heteroaryl-(R^(5b))-heteroaryl, R^(5b)-heterocyclyl and C₃₋₁₄cycloalkyl, and one or two optional substituents each selected from the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl, C₂₋₄alkenyl, haloC₁₋₄alkyl, C₁₋₄alkoxy, C₁₋₄alkoxyC₁₋₄alkoxy, haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio, C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, aminothiocarbonylamino, (C₁₋₄alkyl)₂-amino, aminocarbonyl, C₁₋₄alkylsulfonyl and aminosulfonyl; R^(5a) is one or two optional substituents each selected from the group consisting of halogen, C₁₋₄alkyl, haloC₁₋₄alkyl and C₁₋₄alkoxy; R^(5b) is one or two optional halogen substituents; R⁶ is one optional substituent selected from the group consisting of C₁₋₄alkyl, oxo and aryl; R⁷ is an optional substituent on one, two or three carbon atoms each selected from the group consisting of halogen, C₁₋₄alkyl, C₁₋₄alkoxy, C₁₋₄alkylthio, arylC₁₋₄alkylthio, oxo and aryl, and two optional C₁₋₄alkyl substituents on one carbon atom, and two oxo substituents on a sulfur atom, when said sulfur atom is present; R⁸ is an optional substituent on one carbon atom or an available nitrogen atom selected from the group consisting of R^(8a)-aryl, R^(8a)-arylC₁₋₄alkyl, R^(8a)-arylC₂₋₄alkenyl, R^(8a)-arylC₂₋₄alkynyl, R^(8a)-aryloxy, R^(8a)-aryloxyC₁₋₄alkyl, R^(8a)-arylthio, R^(8a)-arylC₁₋₄alkylthio, R^(8a)-arylC₁₋₄alkylthioC₁₋₄alkyl, R^(8a)-arylsulfonyl, R^(8b)-heteroaryl, R^(8b)-heteroarylC₁₋₄alkyl, R^(8b)-heteroarylthioC₁₋₄alkyl, R^(8b)-heteroarylcarbonylaminoC₁₋₄alkyl and R^(8c)-heterocyclylC₁₋₄alkyl, and an optional C₁₋₄alkyl substituent on an available nitrogen atom, and an optional substituent on one, two or three carbon atoms each selected from the group consisting of halogen, cyano, C₁₋₄alkyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, formyl, C₁₋₄alkoxycarbonyl, C₁₋₄alkylthio and C₁₋₄alkylsulfonyl; R^(8a) is one or two optional substituents each selected from the group consisting of halogen, C₁₋₄alkyl, C₂₋₄alkenyl, haloC₁₋₄alkyl and C₁₋₄alkoxy; R^(8b) is one, two or three optional substituents each selected from the group consisting of halogen, C₁₋₄alkyl and haloC₁₋₄alkyl; R₄ is one substituent selected from the group consisting of hydrogen, C₁₋₄alkyl, carboxyC₁₋₄alkyl, C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, C₁₋₄alkoxycarbonylC₁₋₄alkyl, C₁₋₄alkoxycarbonylC₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonylcarbonyl, aminocarbonyl, R⁹-arylcarbonyl, hydroxysulfonyl, aminosulfonyl, C₁₋₄alkylsulfonyl, hydroxysulfonylC₁₋₄alkylcarbonyl, C₁₋₄alkylsulfonylC₁₋₄alkylcarbonyl, C₁₋₄alkylsulfonylC₁₋₄alkylsulfonyl, C₁₋₄alkoxycarbonylC₁₋₄alkylsulfonyl, R⁹-arylsulfonyl, P[(O)(OH)₂]—C₁₋₄alkyl, R¹⁰-heterocyclylcarbonyl, R¹⁰-heterocyclylsulfonyl, R¹¹-heteroarylcarbonyl, R¹¹-heteroarylC₁₋₄alkylcarbonyl and R¹¹-heteroarylsulfonyl, wherein C₁₋₄alkoxycarbonylC₁₋₄alkylcarbonyl is optionally substituted on C₁₋₄alkyl with (C₁₋₄alkyl)aminoamino; R⁹ is one or two optional substituents each selected from the group consisting of C₁₋₄alkoxy, carboxy and C₁₋₄alkoxycarbonyl; R¹⁰ is an optional (C₁₋₄alkyl)aminoamino substituent on one carbon atom, and two oxo substituents on a sulfur atom, when said sulfur atom is present; and R¹¹ is an optional C₁₋₄alkyl substituent on an available nitrogen atom, and an optional substituent on one carbon atom selected from the group consisting of carboxy and C₁₋₄alkoxycarbonyl.
 4. The compound of claim 1, wherein X₁ and X₂, respectively, are selected from the group consisting of —CH₂— and —CH₂—, —CH₂— and —O—, —CH₂— and —N(R₄)—, —CH₂— and —S—, —C(O)— and —N(R₄)— and —N(R₄)— and —C(O)—; X₃ and X₄, respectively, are —CH₂— and —CH₂—; R₁ is selected from the group consisting of aminoC₁₋₄alkyl, (C₁₋₄alkyl)aminoC₁₋₄alkyl, formylaminoC₁₋₄alkyl, phenylcarbonylaminoC₁₋₄alkyl, aminoimino, hydroxyaminoimino, (C₁₋₄alkyl)aminoimino, (C₁₋₄alkyl)₂-aminoimino and aminoaminoimino, wherein each instance of phenyl is optionally substituted with one or two halogen substituents; R₂ is absent or is one halogen substituent; R³ is hydrogen or is selected from the group consisting of R⁵-phenylC₁₋₄alkyl, carbonyl and sulfonyl, wherein carbonyl and sulfonyl are each substituted with a substituent selected from the group consisting of R⁵-phenyl, R⁵-naphthalenyl, R⁵-phenyl-C₁₋₄alkyl, R⁵-naphthalenyl-C₁₋₄alkyl, R⁶-fluorenyl-C₁₋₄alkyl, R⁵-phenyl-C₁₋₄alkylamino, (R⁵-phenyl)₁₋₂C₁₋₄alkyl, R⁵-phenyl-C₂₋₄alkenyl, R⁵-naphthalenyl-C₂₋₄alkenyl, R⁵-phenylC₂₋₄alkynyl, R⁶-cyclopropyl, R⁶-indanyl, R⁶-1H-indenyl, R⁶-9H-fluorenyl, R⁶—C₃₋₁₄cycloalkylC₁₋₄alkyl, R⁶-9H-fluorenyl-C₁₋₄alkenyl, R⁷-benzo[1,3]dioxolyl, R⁷-4,5-dihydro-benzo[c]thiophenyl, R⁷-4,5,6,7-tetrahydro-benzo[c]thiophenyl, R⁷-4,5,6,7-tetrahydro-benzo[b]thiophenyl, R⁷-chromenyl, R⁷-9H-xanthenyl, R⁷-9H-thioxanthenyl, R⁷-5,6-dihydro-4H-cyclopenta[b]thiophenyl, R⁷-4,5,6,7-tetrahydro-benzofuranyl, R⁷-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophenyl, R⁷-spiro[cyclohexane-1,6′-5,7-dihydro-4H-benzo[b]thiophene], R⁷-benzo[1,3]dioxolyl-C₁₋₄alkyl, R⁷-benzo[1,3]dioxolyl-C₁₋₄alkenyl, R⁷-3H-isobenzofuranyl-C₁₋₄alkenyl, R⁸-furanyl, R⁸-thienyl, R⁸-thiazolyl, R⁸-[1,2,3]thiadiazolyl, R⁸-pyridinyl, R⁸-1H-indolyl, R⁸-benzo[b]furanyl, R⁸-benzo[b]thiophenyl, R⁸-benzo[c]thiophenyl, R⁸-1H-benzoimidazolyl, R⁸-benzothiazolyl, R⁸-thieno[3,2-b]thiophenyl, R⁸-thieno[2,3-b]thiophenyl, R⁸-naphtho[2,1-b]thiophenyl, R⁸-1H-thieno[2,3-c]pyrazolyl, R⁸-imidazo[1,2-a]pyridinyl, R⁸-1H-imidazolyl-C₂₋₄alkenyl, R⁸-furanyl-C₂₋₄alkenyl, R⁸-thienyl-C₂₋₄alkenyl and R⁸-pyridinyl-C₂₋₄alkenyl, wherein each instance of C₂₋₄alkenyl is optionally substituted with one substituent selected from the group consisting of halogen, cyano, C₁₋₄alkylcarbonylamino and aryl; R⁵ is one optional substituent selected from the group consisting of R^(5a)-phenyl, R^(5a)-phenylC₁₋₄alkyl, R^(5a)-phenylC₁₋₄alkoxy, R^(5a)-phenoxy, R^(5a)-phenylcarbonyl, R^(5a)-phenylsulfonylamino, R^(5b)-1H-benzoimidazolyl-C₁₋₄alkyl, R^(5b)-1H-benzoimidazolyl-C₁₋₄alkylcarbonylamino, R^(5b)-thienyl-C₁₋₄alkylcarbonylamino, R^(5b)-pyrimidinylthio, R^(5b)-benzoxazolyl-(R^(5b))-pyrazolyl, R^(5b)-thienyl-(R^(5b))-[1,2,4]oxadiazolyl, R^(5b)-benzo[1,3]dioxolyl and cyclohexyl, and one or two optional substituents each selected from the group consisting of halogen, hydroxy, cyano, nitro, C₁₋₄alkyl, C₂₋₄alkenyl, haloC₁₋₄alkyl, C₁₋₄alkoxy, C₁₋₄alkoxyC₁₋₄alkoxy, haloC₁₋₄alkoxy, C₁₋₄alkylthio, haloC₁₋₄alkylthio, C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, aminothiocarbonylamino, (C₁₋₄alkyl)₂-amino, aminocarbonyl, C₁₋₄alkylsulfonyl and aminosulfonyl; R^(5a) is one or two optional substituents each selected from the group consisting of halogen, C₁₋₄alkyl, haloC₁₋₄alkyl and C₁₋₄alkoxy; R^(5b) is one or two optional halogen substituents; R⁶ is one optional substituent selected from the group consisting of C₁₋₄alkyl, oxo and phenyl; R⁷ is an optional substituent on one, two or three carbon atoms each selected from the group consisting of halogen, C₁₋₄alkyl, C₁₋₄alkoxy, C₁₋₄alkylthio, arylC₁₋₄alkylthio, oxo and phenyl, and two optional C₁₋₄alkyl substituents on one carbon atom, and two optional oxo substituents on a sulfur atom, when said sulfur atom is present; R⁸ is an optional substituent on one carbon atom or an available nitrogen atom selected from the group consisting of R^(8a)-phenyl, R^(8a)-phenylC₁₋₄alkyl, R^(8a)-phenylC₂₋₄alkenyl, R^(8a)-phenylC₂₋₄alkynyl, R^(8a)-naphthalenylC₂₋₄alkynyl, R^(8a)-phenoxy, R^(8a)-phenoxyC₁₋₄alkyl, R^(8a)-phenylthio, R^(8a)-arylC₁₋₄alkylthio, R^(8a)-phenylC₁₋₄alkylthioC₁₋₄alkyl, R^(8a)-phenylsulfonyl, R^(8b)-pyridinyl, R^(8b)-pyrazolyl, R^(8b)-thienyl, R^(8b)-thiazolyl, R^(8b)-pyrazolylC₁₋₄alkyl, R^(8b)-pyrimidinylthioC₁₋₄alkyl, R^(8b)-furanylcarbonylaminoC₁₋₄alkyl and R^(8c)-morpholinylC₁₋₄alkyl, and an optional C₁₋₄alkyl substituent on an available nitrogen atom, and an optional substituent on one, two or three carbon atoms each selected from the group consisting of halogen, cyano, C₁₋₄alkyl, haloC₁₋₄alkyl, hydroxyC₁₋₄alkyl, C₁₋₄alkoxy, formyl, C₁₋₄alkoxycarbonyl, C₁₋₄alkylthio and C₁₋₄alkylsulfonyl; R^(8a) is one or two optional substituents each selected from the group consisting of halogen, C₁₋₄alkyl, C₂₋₄alkenyl, haloC₁₋₄alkyl and C₁₋₄alkoxy; R^(8b) is one, two or three optional substituents each selected from the group consisting of halogen, C₁₋₄alkyl and haloC₁₋₄alkyl; R₄ is one substituent selected from the group consisting of hydrogen, C₁₋₄alkyl, carboxyC₁₋₄alkyl, C₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonyl, C₁₋₄alkoxycarbonylC₁₋₄alkyl, C₁₋₄alkoxycarbonylC₁₋₄alkylcarbonyl, C₁₋₄alkoxycarbonylcarbonyl, aminocarbonyl, R⁹-phenyl-C₁₋₄alkyl, R⁹-phenyl-carbonyl, hydroxysulfonyl, aminosulfonyl, C₁₋₄alkylsulfonyl, hydroxysulfonylC₁₋₄alkylcarbonyl, C₁₋₄alkylsulfonylC₁₋₄alkylcarbonyl, C₁₋₄alkylsulfonylC₁₋₄alkylsulfonyl, C₁₋₄alkoxycarbonylC₁₋₄alkylsulfonyl, R⁹-phenyl-sulfonyl, P[(O)(OH)₂]—C₁₋₄alkyl, R¹⁰-heterocyclylcarbonyl, R¹⁰-tetrahydrothienyl-sulfonyl, R¹¹-1H-tetrazolyl-carbonyl, R¹¹-1H-tetrazolyl-C₁₋₄alkylcarbonyl and R¹¹-1H-imidazolyl-sulfonyl, R¹¹-furanyl-sulfonyl, R¹¹-thienyl-sulfonyl, wherein C₁₋₄alkoxycarbonylC₁₋₄alkylcarbonyl is optionally substituted on C₁₋₄alkyl with (C₁₋₄alkyl)aminoamino; R⁹ is one or two optional substituents each selected from the group consisting of C₁₋₄alkoxy, carboxy and C₁₋₄alkoxycarbonyl; R¹⁰ is an optional (C₁₋₄alkyl)aminoamino substituent on one carbon atom, and two oxo substituents on a sulfur atom, when said sulfur atom is present; and R¹¹ is an optional C₁₋₄alkyl substituent on an available nitrogen atom, and an optional substituent on one carbon atom selected from the group consisting of carboxy and C₁₋₄alkoxycarbonyl.
 5. The compound of claim 1, wherein X₁ and X₂, respectively, are selected from the group consisting of —CH₂— and —CH₂—, —CH₂— and —O—, —CH₂— and —N(R₄)— and —N(R₄)— and —C(O)—; X₃ and X₄, respectively, are —CH₂— and —CH₂—; R₁ is selected from the group consisting of aminoC₁₋₄alkyl and aminoimino, R₂ is absent; R³ is carbonyl substituted with a substituent selected from the group consisting of R⁵-aryl, R⁷-heterocyclyl and R⁸-heteroaryl; R⁵ is heteroaryl-heteroaryl, and an optional aminocarbonyl substituent; R⁷ is an optional substituent on one or two carbon atoms each selected from the group consisting of C₁₋₄alkylthio, arylC₁₋₄alkylthio and oxo; R⁸ is an optional substituent on one carbon atom selected from the group consisting of R^(8a)-aryl, R^(8a)-arylC₂₋₄alkynyl and R^(8a)-arylC₁₋₄alkylthio, and an optional substituent on one, two or three carbon atoms each selected from the group consisting of halogen, C₁₋₄alkyl, C₁₋₄alkoxy and C₁₋₄alkylthio; R^(8a) is one or two optional substituents each selected from the group consisting of halogen and C₁₋₄alkyl; R₄ is one substituent selected from the group consisting of hydrogen, aminosulfonyl, C₁₋₄alkylsulfonyl and arylsulfonyl.
 6. The compound of claim 1, wherein X₁ and X₂, respectively, are selected from the group consisting of —CH₂— and —CH₂—, —CH₂— and —O—, —CH₂— and —N(R₄)— and —N(R₄)— and —C(O)—; X₃ and X₄, respectively, are —CH₂— and —CH₂—; R₁ is selected from the group consisting of aminoC₁₋₄alkyl and aminoimino, R₂ is absent; R³ is carbonyl substituted with a substituent selected from the group consisting of R⁵-phenyl, R⁷-4,5-dihydro-benzo[c]thiophenyl, R⁷-4,5,6,7-tetrahydro-benzo[c]thiophenyl, R⁸-furanyl, R⁸-thienyl, R⁸-pyridinyl and R⁸-benzo[c]thiophenyl; R⁵ is thienyl-[1,2,4]oxadiazolyl, and an optional aminocarbonyl substituent; R⁷ is an optional substituent on one or two carbon atoms each selected from the group consisting of C₁₋₄alkylthio, phenylC₁₋₄alkylthio and oxo; R⁸ is an optional substituent on one carbon atom selected from the group consisting of R^(8a)-phenyl, R^(8a)-phenylC₂₋₄alkynyl and R^(8a)-phenylC₁₋₄alkylthio, and an optional substituent on one, two or three carbon atoms each selected from the group consisting of halogen, C₁₋₄alkyl, C₁₋₄alkoxy and C₁₋₄alkylthio; R^(8a) is one or two optional substituents each selected from the group consisting of halogen and C₁₋₄alkyl; R₄ is one substituent selected from the group consisting of hydrogen, aminosulfonyl, C₁₋₄alkylsulfonyl and arylsulfonyl.
 7. The compound of claim 1, wherein X₁ and X₂, respectively, are selected from the group consisting of —CH₂— and —CH₂—, —CH₂— and —O—, —CH₂— and —N(R₄)— and —N(R₄)— and —C(O)—; X₃ and X₄, respectively, are —CH₂— and —CH₂—; R₁ is selected from the group consisting of aminomethyl and aminoimino, R₂ is absent; R³ is carbonyl substituted with a substituent selected from the group consisting of R⁵-phenyl, R⁷-4,5-dihydro-benzo[c]thiophenyl, R⁷-4,5,6,7-tetrahydro-benzo[c]thiophenyl, R⁸-furanyl, R⁸-thienyl, R⁸-pyridinyl and R⁸-benzo[c]thiophenyl; R⁵ is thienyl-[1,2,4]oxadiazolyl, and an optional aminocarbonyl substituent; R⁷ is an optional substituent on one or two carbon atoms each selected from the group consisting of methylthio, butylthio, phenylmethylthio and oxo; R⁸ is an optional substituent on one carbon atom selected from the group consisting of R^(8a)-phenyl, R^(8a)-phenylethynyl and R^(8a)-phenylmethylthio, and an optional substituent on one, two or three carbon atoms each selected from the group consisting of bromo, methyl, methoxy, propoxy and methylthio; R^(8a) is one or two optional substituents each selected from the group consisting of chloro, fluoro and methyl; and R₄ is one substituent selected from the group consisting of hydrogen, aminosulfonyl, methylsulfonyl and phenylsulfonyl.
 8. The compound of claim 1, wherein X₁ and X₂, respectively, are selected from the group consisting of —CH₂— and —CH₂—, —CH₂— and —O—, —CH₂— and —N(R₄)— and —N(R₄)— and —C(O)—; X₃ and X₄, respectively, are —CH₂— and —CH₂—; R₁ is selected from the group consisting of aminomethyl and aminoimino; R₂ is absent; R³ is selected from the group consisting of (5-phenylethynyl-furan-2-yl)carbonyl, [5-(2-fluoro-phenylethynyl)-furan-2-yl]carbonyl, [5-(2-chloro-phenylethynyl)-furan-2-yl]carbonyl, [4-phenylethynyl-pyridin-2-yl]carbonyl, [5-(2-methyl-phenylethynyl)-furan-2-yl]carbonyl, [5-(4-methyl-phenylethynyl)-furan-2-yl]carbonyl, [5-(2,5-dimethyl-phenylethynyl)-furan-2-yl]carbonyl, (3-benzylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl, (3-butylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl, (3-methylthio-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl, (3-methylthio-7-hydro-6H-benzo[c]thien-1-yl)carbonyl, (3-methylthio-benzo[c]thien-1-yl)carbonyl, (3-methylthio-4-methoxy-benzo[c]thien-1-yl)carbonyl, (3-benzylthio-benzo[c]thien-1-yl)carbonyl, (3-benzylthio-7-hydro-6H-benzo[c]thien-1-yl)carbonyl, (3-thien-2-yl-[1,2,4]oxadiazol-5-yl)carbonyl, [3-(3-thien-2-yl-[1,2,4]oxadiazol-5-yl)-5-aminocarbonyl-phenyl]carbonyl and (3-methyl-4-bromo-5-propoxy-thien-2-yl)carbonyl; and R₄ is one substituent selected from the group consisting of hydrogen, aminosulfonyl, methylsulfonyl and phenylsulfonyl.
 9. A compound selected from the group consisting of 1-(3,4-dichlorophenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 5′-(3,4-dichlorophenylcarbonylaminomethyl)-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-benzoyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-aminothiocarbonylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-benzoyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(9-oxo-10,10-dioxo-thioxanthen-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(9-oxo-fluoren-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-benzoimidazol-1-ylmethylcarbonylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-benzoimidazol-1-ylmethyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-aminosulfonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(4-chloro-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-chloro-benzo[b]-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(1-phenyl-2-methyl-benzoimidazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[4-(3-trifluoromethyl-phenyl)-phenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-benzothiazol-6-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-{4-[(4-benzoxazol-2-yl)-pyrazol-1-yl]-phenyl}carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-phenylsulfonylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-thien-2-ylmethylcarbonylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-benzodioxol-5-yl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[3-(5-chloro-pyrimidin-2-yl)thiophenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-trifluoromethyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[(5-phenylthio)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4-dimethyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methyl-4-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4-difluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-chloro-4-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-chloro-4-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-bromo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methyl-4-bromo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-bromo-4-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-bromo-4-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-nitro-4-bromo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-iodo-4-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-fluoro-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-phenylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-cyclohexylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(trans-4-methyl-cyclohexyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4-dimethoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-methylthio-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-fluoro-4-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-trifluoromethyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-iodo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-iodo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-iodo-4-methyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methyl-4-iodo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-iodo-4-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-dimethylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-dimethylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methylthio-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-methoxycarbonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-bromo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-trifluoromethoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-trifluoromethoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-phenoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-trifluoromethylthio-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[3-(4-methoxy-phenyl)-phenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminoiminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-cyano-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-methylcarbonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-benzodioxol-5-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-chloromethyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-naphthalen-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-trifluoromethyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methylsulfonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-cyclohexyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-trifluoromethyl-4-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-benzyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-benzyloxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (Z)-1-(5-phenylethenyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-benzylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-phenethylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-fluoro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-chloro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4-difluoro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-chloro-phenethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-naphthalen-2-ylmethylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-trifluoromethyl-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4-dichloro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-bromo-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-phenoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methyl-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-fluoro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-chloro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-phenyl-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-bromo-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-methoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-bromo-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-iodo-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-iodo-phenethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methyl-phenethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-benzodioxol-5-ylmethylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methoxy-phenethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methyl-4-methoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methylthio-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(benzodioxol-5-ylethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4-dimethoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methoxy-4-benzyloxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenethyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(phenylethynyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-benzothien-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3,4-difluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(naphthalene-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-phenoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3,4-dichloro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(4-phenyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(2,4-dimethyl-thiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(6-methyl-imidazo[1,2-a]pyridin-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-pyridin-2-yl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(2-pyridin-3-yl-thiazol-4-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(2-pyridin-4-yl-thiazol-4-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(2-phenyl-4-methyl-thiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(2-pyridin-3-yl-4-methyl-thiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[2-(4-methyl-phenyl)-4-methyl-thiazol-5-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(6-bromo-naphthalen-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(1-methyl-3-trifluoromethyl-pyrazol-5-yl)-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[2-(4-trifluoromethyl-phenyl)-4-methyl-thiazol-5-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-chloro-5-trifluoromethyl-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(4-methyl-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(4-methoxy-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,5-di-tert-butyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(3-chloro-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(3-trifluoromethyl-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2,4-dichloro-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2,5-dichloro-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(3,4-dichloro-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(3-methyl-4-chloro-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(4-bromo-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(trans-2-phenyl-cyclopropyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenyl-pyridin-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-thien-2-yl-pyridin-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(3-methoxy-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(4-chloro-pyrazol-1-ylmethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-chloro-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(benzylthiomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(4,6-dimethyl-pyrimidin-2-ylthiomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(3,5-dichloro-phenoxy)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(3,5-dimethyl-4-bromo-pyrazol-1-yl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(5-trifluoromethyl-pyridin-2-ylthiomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[4-phenylethynyl-pyridin-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-methyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(4-fluoro-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2,5-dimethyl-furan-3-yl-carbonylaminomethyl)-furan-2-yl]carbonyl-5-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-chloro-4-isopropylsulfonyl-5-methylthio-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4-dichloro-benzyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-thien-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-benzo[b]furan-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3-fluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (Z)-1-(1-fluoro-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5,6,7-trihydro-4H-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3-chloro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(4-chloro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-chloro-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3-trifluoromethoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-fluoro-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-methylsulfonyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(4-methyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-chloro-6-fluoro-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2,5-dimethyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-methoxy-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2,5-dimethyl-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4-dichloro-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(3,5-difluoro-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-naphthalen-1-ylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(4-tert-butyl-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3-methyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(4-methyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (Z)-1-(1-methyl-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(4-fluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (Z)-1-(2-methoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3-methoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(4-methoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(2-chloro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(benzodioxol-5-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(naphthalen-1-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(1-oxo-2-fluoren-9-ylidene-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(1-phenyl-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(2-methyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(1-methyl-3H-inden-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(1-methyl-indol-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(2-methoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(2,6-difluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(2-oxo-(2H)-chromen-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(8-methoxy-(2H)-chromen-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-bromo-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(2-bromo-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-trifluoromethyl-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[3-(4-methoxy-phenyl)-4-cyano-5-methylthio-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[3-(4-chloro-phenyl)-4-cyano-5-methylthio-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-thieno[3,2-b]thien-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (Z)-1-(1-methylcarbonylamino-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-methyl-thiazol-4-yl)-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-chloro-6-methyl-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[3-(2-methyl-phenoxy)-benzyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-chloro-6-methoxy-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[3-(2-fluoro-phenoxy)-benzyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-propylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-methoxy-4-propyl-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-bromo-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-benzylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[1-oxo-2-(3-oxo-3H-isobenzofuran-1-ylidene)-ethyl]-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-morpholin-4-ylmethyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-phenyl-[1,2,3]thiadiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methylthio-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methylthio-7-hydro-6H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-methyl-furan-3-yl-carbonylaminomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(3,5-dimethyl-4-chloro-pyrazol-1-yl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methyl-4-oxo-6-phenyl-5,6,7-trihydro-4H-benzo[b]furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-ethylthio-4-oxo-6,6-dimethyl-6,7-dihydro-5H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-methoxy-4-allyl-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-isopropylthio-4-oxo-6,6-dimethyl-6,7-dihydro-5H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4-dimethyl-5-cyano-thieno[2,3-b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(3-methoxy-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methyl-6-phenyl-benzo[b]furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-butylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-chloro-6-bromo-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-sec-butylthio-4-oxo-6,6-dimethyl-6,7-dihydro-5H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-benzylthio-4-oxo-6,6-dimethyl-6,7-dihydro-5H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-thieno[2,3-b]thien-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methylthio-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methylthio-4-methoxy-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-indol-3-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(1-methyl-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-methoxy-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(1-benzyl-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-benzylthio-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-benzylthio-7-hydro-6H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (Z)-1-(furan-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (Z)-1-(imidazol-4-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(pyridin-4-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-formyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5,6-dihydro-4H-cyclopenta[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-methylthio-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(1-cyano-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(7-methyl-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(1-ethyl-7-methyl-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(furan-3-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(pyridin-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(pyridin-3-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(thien-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(thien-3-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-dihydroxymethyl-4-methyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5,6,7,8-tetrahydro-4H-cyclohepta[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-cyano-5-methylthio-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-methyl-5-bromo-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], spiro[cyclohexane-1,6′-5,7-dihydro-4H-benzo[b]thiophene]-2′-carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-ethoxy-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4-dichlorophenyl)carbonyl-2-oxo-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-benzylaminocarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-hydroxy-phenylethynyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3-hydroxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-tert-butyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-methoxycarbonyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(4-tert-butyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-fluoren-1-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(9-oxo-fluoren-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-chloro-6-ethyl-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(2-hydroxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-aminocarbonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-tert-butyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4,5-trichloro-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-trifluoromethyl-6-methyl-1H-thieno[2,3-c]pyrazol-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-thien-2-yl-[1,2,4]oxadiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4,5-dibromo-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[4-(3,5-bis-trifluoromethyl-phenoxy)-phenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4-dichlorophenyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3-benzyloxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(4-tert-butyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(1-phenylsulfonyl-1H-indol-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[3-(3-thien-2-yl-[1,2,4]oxadiazol-5-yl)-5-aminocarbonyl-phenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-1H-indol-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-3H-inden-1-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-oxo-indan-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-phenyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-fluoren-9-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(1-oxo-2,2-diphenyl-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-[3-(2-methoxy-ethoxy)-phenylethenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-9H-xanthen-9-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-9H-xanthen-9-ylmethylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3-phenethoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-phenyl-5-trifluoromethyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-phenylethynylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan]-5′-[methyl-(trimethyl)ammonium], 1-(1-chloro-naphtho[2,1-b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[3-(4-chloro-phenyl)-5-methylthio-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(4-benzyloxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-[3-(3-methoxy-propoxy)-phenylethenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-[3-(2-ethoxy-ethoxy)-phenylethenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methyl-4-bromo-5-propoxy-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-formylaminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminosulfonylaminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-[hydroxyamino(imino)methyl]-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-[hydrazino(imino)methyl]-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4-dichlorophenyl)carbonyl-5′-aminomethyl-6′-fluoro-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(2-fluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-[methylamino(imino)methyl]-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-6′-fluoro-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(2,3-difluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-[dimethylamino(imino)methyl]-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminoethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4-dichlorophenyl)carbonyl-2′-oxo-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-oxo-2′-(2,4-dimethoxy-benzyl)-5′-aminomethyl-spiro[piperidine-4,3′-1H-isoindole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-oxo-5′-aminomethyl-spiro[piperidine-4,3′-1H-isoindole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-spiro[piperidine-4,3′-indane], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-ethyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(2-methoxycarbonyl-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(2-carboxy-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-methoxycarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(4-carboxy-phenyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-aminocarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole]-1′-(2-ethyl-phosphonic acid), 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-hydroxysulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(3-methoxycarbonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(2-ethoxy-1,2-dioxo-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(2-1H-tetrazol-5-yl-1-oxo-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(3-carboxy-phenyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-[4-ethoxy-2-(methylamino)amino-1,4-dioxo-butyl]-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(methylsulfonylmethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(1H-tetrazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(hydroxysulfonylmethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(1-methyl-imidazol-4-yl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(5-carboxy-furan-2-yl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-[5-(N′-methyl-hydrazino)-1,1-dioxo-3,4,5-trihydro-(2H)-thien-3-yl]sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-methylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-methylsulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-phenylsulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-aminosulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-[(methoxycarbonyl)methyl]-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(3-methoxycarbonyl-phenyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(5-methoxycarbonyl-furan-2-yl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(3-methyl-4-bromo-5-propoxy-thien-2-yl)carbonyl-1′-hydroxysulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(5-carboxy-thien-3-yl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(methylsulfonylmethyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(N′-methylhydrazino-carbonylmethyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(3-methylthio-benzo[c]thien-1-yl)carbonyl-1′-hydroxysulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(4,5-dibromo-thien-2-yl)carbonyl-1′-hydroxysulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(3,4-dichlorophenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(1,1-dioxo-(2H)-benzo[b]thiophene)], 1-(3,4-dichlorophenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]thiophene], 1-(2,2-diphenylethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(9H-fluoren-9-ylmethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3-methyl-thien-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[4-(4-chloro-phenyl)-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-thien-2-ylsulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], and 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-thien-3-ylsulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole].
 10. The compound of claim 9, wherein 1-(3,4-dichlorophenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-benzoyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-aminothiocarbonylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(9-oxo-10,10-dioxo-thioxanthen-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(4-chloro-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-benzothiazol-6-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-{4-[(4-benzoxazol-2-yl)-pyrazol-1-yl]-phenyl}carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-thien-2-ylmethylcarbonylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-benzodioxol-5-yl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[3-(5-chloro-pyrimidin-2-yl)thiophenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[(5-phenylthio)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4-dimethyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methyl-4-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4-difluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-chloro-4-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-chloro-4-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-bromo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methyl-4-bromo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-bromo-4-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-bromo-4-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-nitro-4-bromo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-iodo-4-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-fluoro-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-phenylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-cyclohexylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(trans-4-methyl-cyclohexyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4-dimethoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-methylthio-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-fluoro-4-chloro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-trifluoromethyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-iodo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-iodo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-iodo-4-methyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methyl-4-iodo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-iodo-4-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-methoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-dimethylamino-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methylthio-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-methoxycarbonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-bromo-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-phenoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-trifluoromethylthio-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[3-(4-methoxy-phenyl)-phenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5-aminoiminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-benzodioxol-5-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-naphthalen-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-trifluoromethyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methylsulfonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-trifluoromethyl-4-fluoro-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-benzyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-benzyloxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (Z)-1-(5-phenylethenyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4-dichloro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-phenoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-fluoro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-chloro-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-phenyl-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-bromo-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-methoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-iodo-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-benzodioxol-5-ylmethylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methyl-4-methoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methylthio-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4-dimethoxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methoxy-4-benzyloxy-benzyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenethyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(phenylethynyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-benzothien-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3,4-difluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(naphthalene-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-phenoxy-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3,4-dichloro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(4-phenyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(2,4-dimethyl-thiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-pyridin-2-yl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(2-pyridin-3-yl-thiazol-4-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(2-pyridin-4-yl-thiazol-4-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(2-phenyl-4-methyl-thiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(6-bromo-naphthalen-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[2-(4-trifluoromethyl-phenyl)-4-methyl-thiazol-5-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-chloro-5-trifluoromethyl-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(4-methyl-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(4-methoxy-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,5-di-tert-butyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(3-chloro-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(3-trifluoromethyl-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2,4-dichloro-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2,5-dichloro-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(3,4-dichloro-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(3-methyl-4-chloro-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(4-bromo-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(trans-2-phenyl-cyclopropyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenyl-pyridin-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-thien-2-yl-pyridin-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(3-methoxy-phenyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(4-chloro-pyrazol-1-ylmethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-chloro-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(benzylthiomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(4,6-dimethyl-pyrimidin-2-ylthiomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(3,5-dichloro-phenoxy)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(3,5-dimethyl-4-bromo-pyrazol-1-yl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(5-trifluoromethyl-pyridin-2-ylthiomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[4-phenylethynyl-pyridin-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-methyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(4-fluoro-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2,5-dimethyl-furan-3-yl-carbonylaminomethyl)-furan-2-yl]carbonyl-5-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-chloro-4-isopropylsulfonyl-5-methylthio-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-thien-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-benzo[b]furan-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3-fluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (Z)-1-(1-fluoro-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5,6,7-trihydro-4H-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3-chloro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(4-chloro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-chloro-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3-trifluoromethoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-fluoro-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(4-methyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-chloro-6-fluoro-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2,5-dimethyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-methoxy-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2,5-dimethyl-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4-dichloro-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(3,5-difluoro-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-naphthalen-1-ylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(4-tert-butyl-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3-methyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(4-methyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(4-fluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3-methoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(2-chloro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(benzodioxol-5-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(naphthalen-1-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(1-oxo-2-fluoren-9-ylidene-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(1-phenyl-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(2-methyl-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(1-methyl-3H-inden-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(1-methyl-indol-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(2-methoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(2,6-difluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(2-oxo-(2H)-chromen-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(8-methoxy-(2H)-chromen-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-bromo-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(2-bromo-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[3-(4-methoxy-phenyl)-4-cyano-5-methylthio-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[3-(4-chloro-phenyl)-4-cyano-5-methylthio-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-thieno[3,2-b]thien-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (Z)-1-(1-methylcarbonylamino-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-methyl-thiazol-4-yl)-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[3-(2-methyl-phenoxy)-benzyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[3-(2-fluoro-phenoxy)-benzyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-propylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-methoxy-4-propyl-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-bromo-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-benzylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[1-oxo-2-(3-oxo-3H-isobenzofuran-1-ylidene)-ethyl]-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-phenyl-[1,2,3]thiadiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methylthio-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methylthio-7-hydro-6H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-methyl-furan-3-yl-carbonylaminomethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(3,5-dimethyl-4-chloro-pyrazol-1-yl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methyl-4-oxo-6-phenyl-5,6,7-trihydro-4H-benzo[b]furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-ethylthio-4-oxo-6,6-dimethyl-6,7-dihydro-5H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-methoxy-4-allyl-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-isopropylthio-4-oxo-6,6-dimethyl-6,7-dihydro-5H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(3-methoxy-phenoxymethyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methyl-6-phenyl-benzo[b]furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-butylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-chloro-6-bromo-benzo[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-sec-butylthio-4-oxo-6,6-dimethyl-6,7-dihydro-5H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-benzylthio-4-oxo-6,6-dimethyl-6,7-dihydro-5H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-thieno[2,3-b]thien-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methylthio-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methylthio-4-methoxy-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-indol-3-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(1-methyl-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-methoxy-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(1-benzyl-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-benzylthio-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-benzylthio-7-hydro-6H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (Z)-1-(furan-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-formyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5,6-dihydro-4H-cyclopenta[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-methylthio-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(1-cyano-2-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(7-methyl-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(1-ethyl-7-methyl-indol-3-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(thien-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(thien-3-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-dihydroxymethyl-4-methyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5,6,7,8-tetrahydro-4H-cyclohepta[b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-cyano-5-methylthio-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-methyl-5-bromo-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-ethoxy-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3-hydroxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-tert-butyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-methoxycarbonyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(2-hydroxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4,5-trichloro-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-trifluoromethyl-6-methyl-1H-thieno[2,3-c]pyrazol-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-thien-2-yl-[1,2,4]oxadiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4,5-dibromo-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4-dichlorophenyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3-benzyloxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(4-tert-butyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(1-phenylsulfonyl-1H-indol-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[3-(3-thien-2-yl-[1,2,4]oxadiazol-5-yl)-5-aminocarbonyl-phenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-1H-indol-2-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-3H-inden-1-ylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-phenyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(1-oxo-2,2-diphenyl-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-[3-(2-methoxy-ethoxy)-phenylethenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3-phenethoxy-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(4-phenyl-5-trifluoromethyl-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(1-chloro-naphtho[2,1-b]thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[3-(4-chloro-phenyl)-5-methylthio-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-[3-(2-ethoxy-ethoxy)-phenylethenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methyl-4-bromo-5-propoxy-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-formylaminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-[hydroxyamino(imino)methyl]-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-[hydrazino(imino)methyl]-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(2-fluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-[methylamino(imino)methyl]-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-6′-fluoro-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(2,3-difluoro-phenylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-[dimethylamino(imino)methyl]-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3,4-dichlorophenyl)carbonyl-2′-oxo-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-oxo-2′-(2,4-dimethoxy-benzyl)-5′-aminomethyl-spiro[piperidine-4,3′-1H-isoindole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-oxo-5′-aminomethyl-spiro[piperidine-4,3′-1H-isoindole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-spiro[piperidine-4,3′-indane], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-ethyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(2-methoxycarbonyl-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(2-carboxy-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-methoxycarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(4-carboxy-phenyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-aminocarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole]-1′-(2-ethyl-phosphonic acid), 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-hydroxysulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(3-methoxycarbonyl-phenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(2-ethoxy-1,2-dioxo-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(2-1H-tetrazol-5-yl-1-oxo-ethyl)-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(3-carboxy-phenyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-[4-ethoxy-2-(methylamino)amino-1,4-dioxo-butyl]-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(methylsulfonylmethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(1H-tetrazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(hydroxysulfonylmethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(1-methyl-imidazol-4-yl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(5-carboxy-furan-2-yl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-[5-(N′-methyl-hydrazino)-1,1-dioxo-3,4,5-trihydro-(2H)-thien-3-yl]sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-methylcarbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-methylsulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-phenylsulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-aminosulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-[(methoxycarbonyl)methyl]-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(3-methoxycarbonyl-phenyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(5-methoxycarbonyl-furan-2-yl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(3-methyl-4-bromo-5-propoxy-thien-2-yl)carbonyl-1′-hydroxysulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(5-carboxy-thien-3-yl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(methylsulfonylmethyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-(N′-methylhydrazino-carbonylmethyl)sulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(3-methylthio-benzo[c]thien-1-yl)carbonyl-1′-hydroxysulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(4,5-dibromo-thien-2-yl)carbonyl-1′-hydroxysulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(3,4-dichlorophenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]thiophene], 1-(2,2-diphenylethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(9H-fluoren-9-ylmethyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], (E)-1-(3-methyl-thien-2-ylethenyl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[4-(4-chloro-phenyl)-thien-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-thien-2-ylsulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], and 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-thien-3-ylsulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole].
 11. The compound of claim 9, wherein 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-fluoro-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-5′-aminoiminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-chloro-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[4-phenylethynyl-pyridin-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2-methyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(4-methyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[5-(2,5-dimethyl-phenylethynyl)-furan-2-yl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-benzylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methylthio-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methylthio-7-hydro-6H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-butylthio-4-oxo-5,6,7-trihydro-4H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methylthio-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methylthio-4-methoxy-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-benzylthio-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-benzylthio-7-hydro-6H-benzo[c]thien-1-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-thien-2-yl-[1,2,4]oxadiazol-5-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-[3-(3-thien-2-yl-[1,2,4]oxadiazol-5-yl)-5-aminocarbonyl-phenyl]carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(3-methyl-4-bromo-5-propoxy-thien-2-yl)carbonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-benzo[b]furan], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-oxo-5′-aminomethyl-spiro[piperidine-4,3′-1H-isoindole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-spiro[piperidine-4,3′-indane], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-methylsulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-phenylsulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole], and 1-(5-phenylethynyl-furan-2-yl)carbonyl-1′-aminosulfonyl-5′-aminomethyl-spiro[piperidine-4,3′-(2H)-indole].
 12. A method for treating a tryptase mediated inflammatory, vascular or dermatological condition in a subject in need thereof comprising administering to the subject an effective amount of a compound of claim
 1. 13. The method of claim 12, wherein the tryptase mediated inflammatory, vascular or dermatological condition is selected from asthma, allergic rhinitis, rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, gouty arthritis, peptic ulcers, ocular and vernal conjunctivitis, psoriasis, inflammatory bowel disease, Crohn's disease, chronic obstructive pulmonary disease, urticaria, bullous pemphiguoid, schleroderma, fibrosis, dermatitis, psoriasis, pruritis, angioedema, eczematous dermatitis, anaphylaxis, hyperproliferative skin disease, inflammatory skin conditions, hepatic cirrhosis, glomerulonephritis, nephritis, vascular inflammation, atherosclerosis or restenosis.
 14. The method of claim 13, wherein the tryptase mediated inflammatory, vascular or dermatological condition is selected from asthma, allergic rhinitis, inflammatory bowel disease, Crohn's disease or pruritis.
 15. The method of claim 12, wherein the effective amount of the compound of claim 1 is from about 0.001 mg/kg/day to about 300 mg/kg/day. 